Respiratory aspiration during treatment with benzodiazepines, antiepileptic and antidepressant drugs in the pharmacovigilance database from VigiBase.

INTRODUCTION: Three psychotropic drug classes, benzodiazepines, antiepileptic drugs (AEDs) and antidepressants (ADs), whether used in treatment or overdose, may be associated with respiratory aspiration. Polypharmacy was defined by counting suspected drugs from these classes or two others, antipsychotics and opioids. The confounding effects of polypharmacy were considered in this study. AREAS COVERED: VigiBase records of respiratory aspiration associated with benzodiazepines, AEDs, and/or ADs from inception until 5 September 2021, were reviewed. VigiBase, the World Health Organization's global pharmacovigilance database, uses a statistical signal for associations called the information component (IC). EXPERT OPINION: The ICs (and IC025) were benzodiazepines 2.8 (and 2.6), AEDs 1.6 (and 1.5), and ADs 1.4 (and 1.3). The cases of respiratory aspiration associated with at least one drug from these 3 classes included: 1) 553 cases absent any known overdose (2.8 ± 1.7 drugs) and 2) 347 overdose cases (2.9 ± 1.8 drugs). Little support for the association of respiratory aspiration and benzodiazepine, AED or AD monotherapy in therapeutic dosages was found. Studies of the association between benzodiazepine monotherapy and respiration aspiration are needed in geriatric patients. ADs added to other medications increased lethality in all cases of respiratory aspiration including those associated with overdose, polypharmacy and/or major medical problems.

Cristaluria causada por amoxicilina / Crystalluria caused by amoxicillin

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Poor compliance with antimicrobial guidelines for childhood pneumonia.

INTRODUCTION: Antimicrobial stewardship programmes recommend use of narrow-spectrum antibiotics as first-line treatment of childhood pneumonia in secondary care. The primary aim of the present study was to assess whether current guidelines are followed. A secondary aim was to assess if tracheal aspiration is a useful tool in the diagnostic process of suspected childhood pneumonia. METHODS: This was a retrospective descriptive single-centre cohort study. Children between three months and 17 years with a pneumonia diagnosis were included. The children were divided into two groups based on whether or not they had been treated with antibiotics (TWA) by their general practitioner. We obtained information on blood samples, treatment and microbial findings. Finally, we compared the use of antibiotics and the microbiological diagnosis of children TWA prior to admittance with those of drug-naïve children (DN). RESULTS: Guidelines were followed in 55% (n = 78) of the cases, which is comparable to results reported by other studies. Tracheal aspiration culture identified a bacterial pathogen in 54% (n = 77) of the cases; Haemophilus influenzae was the most prevalent. A larger percentage of tracheal aspirations was positive in the TWA group than in the DN group (66%; n = 31 versus 48%; n = 46). CONCLUSIONS: Compliance with local guidelines was comparable to findings reported in similar single-centre studies. Airway aspiration may be a useful supplement to other investigations. FUNDING: none. TRIAL REGISTRATION: not relevant.

Epigallocatechin-3-gallate ameliorates seawater aspiration-induced acute lung injury via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats.

Signal transducers and activators of transcriptions 1 (STAT1) play an important role in the inflammation process of acute lung injury (ALI). Epigallocatechin-3-gallate (EGCG) exhibits a specific and strong anti-STAT1 activity. Therefore, our study is to explore whether EGCG pretreatment can ameliorate seawater aspiration-induced ALI and its possible mechanisms. We detected the arterial partial pressure of oxygen, lung wet/dry weight ratios, protein content in bronchoalveolar lavage fluid, and the histopathologic and ultrastructure staining of the lung. The levels of IL-1, TNF-α, and IL-10 and the total and the phosphorylated protein level of STAT1, JAK1, and JAK2 were assessed in vitro and in vivo. The results showed that EGCG pretreatment significantly improved hypoxemia and histopathologic changes, alleviated pulmonary edema and lung vascular leak, reduced the production of TNF-α and IL-1, and increased the production of IL-10 in seawater aspiration-induced ALI rats. EGCG also prevented the seawater aspiration-induced increase of TNF-α and IL-1 and decrease of IL-10 in NR8383 cell line. Moreover, EGCG pretreatment reduced the total and the phosphorylated protein level of STAT1 in vivo and in vitro and reduced the phosphorylated protein level of JAK1 and JAK2. The present study demonstrates that EGCG ameliorates seawater aspiration-induced ALI via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats.

Bile acids aspiration reduces survival in lung transplant recipients with BOS despite azithromycin.

Azithromycin (AZM) improved bronchiolitis obliterans syndrome (BOS) and reduced aspiration in lung transplant (LTx) recipients. We hypothesize that AZM could improve graft and overall survival more efficiently in LTx patients with BOS who have bile acid (BA) aspiration by protecting against the aspiration-induced progression of BOS. The goal was to compare FEV(1) (% baseline), BOS progression and overall survival in LTx recipients treated with AZM for BOS, both with versus without BA aspiration. Therefore, LTx recipients treated with AZM for BOS were recruited and broncho-alveolar lavage (BAL) samples were analyzed for the presence of BA and neutrophilia before the start of AZM treatment. Short-term effect of AZM on FEV(1) and BAL neutrophilia was assessed, progression of BOS and survival were followed-up for 3 years and results were compared between patients with/without BA aspiration. 19/37 LTx patients had BA in BAL. BA aspiration predisposed to a significantly worse outcome, in terms of decline in FEV(1) , progression of BOS ≥ 1 and survival. AZM does not seem to protect against the long-term allograft dysfunction caused by gastroesophageal reflux (GER) and aspiration and an additional treatment targeting aspiration may be indicated in those LTx patients.

Vagal control of mucociliary clearance in murine lungs: a study in a chronic preparation.

We conducted several experiments that focused on the effect of vagal control on mucociliary clearance (MCC) in murine lungs. We hypothesized that loss of vagal control by chronic denervation (i.e. vagotomy) would reduce both basal MCC and the increase in MCC typically observed upon stimulation of capsaicin sensitive C-fibers. Vagotomy was performed on the right side of C57BL/6 mice and MCC was measured 5 days later. Mucociliary clearance was measured by gamma scintigraphy after oropharyngeal aspiration of the radioisotope (99m)technetium and was expressed as the amount of radioactivity removed from the right lung 6h later. Baseline MCC was unaffected by vagotomy, averaging 6.5+/-4.9% and 6.8+/-5.8%, in 6 vagotomized and 6 non-vagotomized mice (controls), respectively. Mucociliary clearance increased significantly to 12.7+/-5.9% in 9 non-vagotomized mice treated with 1.6 x 10(-9) M capsaicin, a vagally-mediated, nociceptor stimulus (p=0.041). Capsaicin was admixed with (99m)technetium and administered by oropharyngeal aspiration. In contrast, MCC was unchanged from control values in 9 vagotomized, capsaicin-treated animals, averaging 6.0+/-5.5% (p=0.024). These findings suggest that loss of vagal control through denervation does not affect basal MCC in C57BL/6 mice, but does appear to reduce the capacity of mice to respond to nociceptor agents that stimulate MCC. These data could have implications for patients whose lungs are denervated due to lung transplantation, since they may be at risk for an inadequate MCC response to inhaled irritants and inflammatory mediators, which are also nociceptor stimuli.

Effects of Nigella sativa seed extract on ameliorating lung tissue damage in rats after experimental pulmonary aspirations.

Aspiration of gastric contents can cause serious lung injury, although the mechanisms of pulmonary damage are still not clear and means of amelioration of the pulmonary damage have been little investigated. The black cumin seed, Nigella sativa L. (NS) has been shown to have specific health benefits and the aim of the current study was to investigate the possible beneficial effects of NS on experimental lung injury in male Wistar rats after pulmonary aspiration of different materials. The rats were randomly allotted into one of six experimental groups (n=7 per group): (1) saline control, (2) saline+NS treated, (3) Pulmocare (a specialized nutritional supplement given to pulmonary patients), (4) Pulmocare+NS treated, (5) hydrochloric acid, (6) hydrochloric acid+NS treated. The saline, Pulmocare and hydrochloric acid were injected into the lungs in a volume of 2 ml/kg. The rats received daily oral doses of NS volatile oil (400mg/kg body weight) by means of intragastric intubation for 7 days starting immediately after the pulmonary aspiration of the materials. After 7 days, the rats were sacrificed and tissue samples from both lungs were taken for histopathological investigation. To date, no similar study investigating the potential for NS treatment to protect against lung injury after pulmonary aspiration of materials has been reported. Our study showed that NS treatment inhibits the inflammatory pulmonary responses, reducing significantly (p<0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar macrophages, interstitial fibrosis, granuloma and necrosis formation in different pulmonary aspiration models. Our data indicate a significant reduction in the activity of inducible nitric oxide synthase (iNOS) and a rise in surfactant protein D in lung tissue of different pulmonary aspiration models after NS therapy. Based on our results, we conclude that NS treatment might be beneficial in lung injury and have potential clinical use.

Use of natural surfactant in an infant with aspiration syndrome.

The remarkable effectiveness of surfactant in neonatology suggested its use also in adults as well as in children on the basis of the pulmonary pathophysiology. We describe a case of an 18 month-old child affected by acute respiratory distress syndrome (ARDS) due to asphyxy by gastric juice inhalation, successfully treated with porcine surfactant (Curosurf) associated with ventilatory therapy.