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Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents.

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Introduction: the incidence of Respiratory Syncytial Virus (RSV) infection and their variability in the clinical management, make this disease a candidate for monitoring adequate use of resources. The objective of this study was to evaluate the impact of the updating of clinical guidelines for RSV bronchiolitis on the use of diagnostic testing and medications in tertiary hospitals in Colombia. Methods: we performed a cross-sectional study, evaluating the frequencies of drug prescription and medical tests, before (January-December 2016) and after (January to December 2019) of updating and dissemination of a new protocol for the treatment of RSV bronchiolitis in two tertiary hospitals in Colombia. Results: a total of 108 patients with RSV bronchiolitis were included. The demographic characteristics and clinical manifestations were similar in both groups. The length of hospital stays was similar in both groups. We did not find statistically significant differences in the frequency of medical tests. There was a decrease in the use of salbutamol (67.3% pre-protocol vs 51.8% post-protocol; P < .01). There were also significant reductions in the use of nebulized hypertonic saline solution (91.6% vs 82.6% P = 0.004). Conclusion: our results demonstrate that the updating of clinical guidelines for RSV bronchiolitis was effective, as it achieved decreases in the use of bronchodilators and nebulized hypertonic saline solution. It is necessary to continue developing new strategies targeted to increase adherence to guidelines and evaluate the impact on the use of resources.

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OBJECTIVE: To investigate the efficacy and safety of nebulized poractant alfa (at 200 and 400 mg/kg doses) delivered in combination with nasal continuous positive airway pressure compared with nasal continuous positive airway pressure alone in premature infants with diagnosed respiratory distress syndrome. STUDY DESIGN: This randomized, controlled, multinational study was conducted in infants at 280/7 to 326/7 weeks of gestation. The primary outcome was the incidence of respiratory failure in the first 72 hours of life, defined as needing endotracheal surfactant and/or mechanical ventilation owing to prespecified criteria. Secondary outcomes included the time to respiratory failure in the first 72 hours, duration of ventilation, mortality, incidence of bronchopulmonary dysplasia, and major associated neonatal comorbidities. In addition, the safety and tolerability of the treatments were assessed reporting the number and percentage of infants with treatment-emergent adverse events and adverse drug reactions during nebulization. RESULTS: In total, 129 infants were randomized. No significant differences were observed for the primary outcome: 24 (57%), 20 (49%), and 25 (58%) infants received endotracheal surfactant and/or mechanical ventilation within 72 hours in the poractant alfa 200 mg/kg, poractant alfa 400 mg/kg, and nasal continuous positive airway pressure groups, respectively. Similarly, secondary respiratory outcomes did not differ among groups. Enrollment was halted early owing to a change in the benefit-risk balance of the intervention. Nebulized poractant alfa was well-tolerated and safe, and no serious adverse events were related to the study treatment. CONCLUSIONS: The intervention did not decrease the likelihood of respiratory failure within the first 72 hours of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03235986.

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INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic and progressive disease characterized by the permanent destruction of small and mid-sized airways. Many patients are chronically colonized by Pseudomona aueruginosa, for which oral antibiotics are given. Evidence to support the use of inhaled antibiotics is contradictory. OBJECTIVE: To describe the clinical effects of inhaled Tobramycin in P. aeruginosa density in sputum and eradication, lung function, bacterial resistance, and exacerbations requiring hospital admission, in the context of patients with NCFBE colonized by P. aeruginosa. METHODS: We included RCTs comparing inhaled tobramycin to other antibiotics and placebo in patients with NCFBE. MAIN FINDINGS: 5 studies with 211 participants were included. 2 studies reported a significant but transitory decrease in P. aeruginosa density in sputum as compared to placebo. There was a small difference in the eradication of P. aeruginosa among groups, although with very wide confidence intervals. Tobramycin reduced the rate of hospital admissions but no frequency of exacerbations. There was no evidence of an increased rate of bacterial resistance but was associated to respiratory adverse effects. CONCLUSIONS: Evidence is not robust enough to confirm a benefit of inhaled Tobramycin in reducing P. aeruginosa sputum density or eradication. There was a high attrition rate, in part due to respiratory adverse events after drug administration, which affects interpretation of the data and raises concerns about the tolerability of the drug. Further network meta-analysis should be done to compare the efficacy and safety of different inhaled antibiotics.

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International guidelines have recommended the use of inhaled beta-2 agonists and systemic corticosteroids (SCs) as the first-line treatment for acute asthma. OBJECTIVE: To evaluate the evidence for the efficacy of inhaled corticosteroids (ICSs) in addition to SCs compared to SCs alone in children with acute asthma in the emergency department (ED) or during hospitalization. DATA SOURCES: Five electronic databases were searched. STUDY SELECTION: All randomized clinical trials that compared ICS (via nebulizer or metered dose inhaler) plus SC (oral or parenteral) with placebo (or standard care) plus SC were included without language restriction. DATA EXTRACTION: Two reviewers independently reviewed all the studies. The primary outcomes were hospital admission and hospital length of stay (LOS), and secondary outcomes were readmissions during follow-up, ED-LOS, lung function, asthma clinical score, oxygen saturation, and heart and respiratory rates. RESULTS: Nine studies (n = 1473) met the inclusion criteria. In all the studies, the ICS was budesonide. Compared to SC alone, adding budesonide to SC did not affect hospitalization rate, but decreased hospital LOS by more than 1 day (MD = -29.08 hours [-39.9 to -18.3]; I2 = 0%, P = < .00001). Moreover, adding budesonide significantly improved the acute asthma severity score among patients at ED. CONCLUSIONS: Compared to SC alone, adding budesonide to SC does not affect the hospitalization rate, but decreases the LOS and improves the acute asthma score in children in an ED setting.

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OBJECTIVES: The administration of ketamine as nebulized inhalation is relatively new and studies on nebulized ketamine are scarce. We aimed to investigate the analgesic efficacy of nebulized ketamine (1 and 2mg.kg-1) administered 30min before general anesthesia in children undergoing elective tonsillectomy in comparison with intravenous ketamine (0.5mg.kg-1) and saline placebo. METHODS: One hundred children aged (7-12) years were randomly allocated in four groups (n=25) receive; Saline Placebo (Group C), Intravenous Ketamine 0.5mg.kg-1 (Group K-IV), Nebulized Ketamine 1mg.kg-1 (Group K-N1) or 2mg.kg-1 (Group K-N2). The primary endpoint was the total consumption of rescue analgesics in the first 24h postoperative. RESULTS: The mean time to first request for rescue analgesics was prolonged in K-N1 (400.9±60.5min, 95% CI 375.9-425.87) and K-N2 (455.5±44.6min, 95% CI 437.1-473.9) groups compared with Group K-IV (318.5±86.1min, 95% CI 282.9-354.1) and Group C (68.3±21.9min, 95% CI 59.5-77.1; p<0.001), with a significant difference between K-N1 and K-N2 Groups (p<0.001). The total consumption of IV paracetamol in the first 24h postoperative was reduced in Group K-IV (672.6±272.8mg, 95% CI 559.9-785.2), Group K-N1 (715.6±103.2mg, 95% CI 590.4-840.8) and Group K-N2 (696.6±133.3mg, 95% CI 558.8-834.4) compared with Control Group (1153.8±312.4mg, 95% CI 1024.8-1282.8; p<0.001). With no difference between intravenous and Nebulized Ketamine Groups (p=0.312). Patients in intravenous and Nebulized Ketamine Groups showed lower postoperative VRS scores compared with Group C (p<0.001), no differences between K-IV, K-N1 or K-N2 group and without significant adverse effects. CONCLUSION: Preemptive nebulized ketamine was effective for post-tonsillectomy pain relief. It can be considered as an effective alternative route to IV ketamine.

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Abstract Objectives The administration of ketamine as nebulized inhalation is relatively new and studies on nebulized ketamine are scarce. We aimed to investigate the analgesic efficacy of nebulized ketamine (1 and 2 mg.kg-1) administered 30 min before general anesthesia in children undergoing elective tonsillectomy in comparison with intravenous ketamine (0.5 mg.kg-1) and saline placebo. Methods One hundred children aged (7-12) years were randomly allocated in four groups (n = 25) receive; Saline Placebo (Group C), Intravenous Ketamine 0.5 mg.kg-1 (Group K-IV), Nebulized Ketamine 1 mg.kg-1 (Group K-N1) or 2 mg.kg-1 (Group K-N2). The primary endpoint was the total consumption of rescue analgesics in the first 24 h postoperative. Results The mean time to first request for rescue analgesics was prolonged in K-N1 (400.9 ± 60.5 min, 95% CI 375.9-425.87) and K-N2 (455.5 ± 44.6 min, 95% CI 437.1-473.9) groups compared with Group K-IV (318.5 ± 86.1 min, 95% CI 282.9-354.1) and Group C (68.3 ± 21.9 min, 95% CI 59.5-77.1; p < 0.001), with a significant difference between K-N1 and K-N2 Groups (p < 0.001). The total consumption of IV paracetamol in the first 24 h postoperative was reduced in Group K-IV (672.6 ± 272.8 mg, 95% CI 559.9-785.2), Group K-N1 (715.6 ± 103.2 mg, 95% CI 590.4-840.8) and Group K-N2 (696.6 ± 133.3 mg, 95% CI 558.8-834.4) compared with Control Group (1153.8 ± 312.4 mg, 95% CI 1024.8-1282.8; p < 0.001). With no difference between intravenous and Nebulized Ketamine Groups (p = 0.312). Patients in intravenous and Nebulized Ketamine Groups showed lower postoperative VRS scores compared with Group C (p < 0.001), no differences between K-IV, K-N1 or K-N2 group and without significant adverse effects. Conclusion Preemptive nebulized ketamine was effective for post-tonsillectomy pain relief. It can be considered as an effective alternative route to IV ketamine.

Resumo Objetivos A administração de cetamina por via inalatória através de nebulizador é relativamente nova e os estudos sobre este assunto são escassos. Nosso objetivo foi investigar a eficácia analgésica da cetamina nebulizada (1 e 2 mg.kg-1) administrada 30 minutos antes da anestesia geral em crianças submetidas à amigdalectomia eletiva, em comparação com cetamina intravenosa (0,5 mg.kg-1) e placebo (soro fisiológico). Métodos Cem crianças entre 7-12 anos foram randomicamente alocadas em quatro grupos (n = 25) e receberam: soro fisiológico para controle (Grupo C); 0,5 mg.kg-1 de cetamina intravenosa (Grupo C-IV); 1 mg.kg-1 de cetamina nebulizada (Grupo C-N1); 2 mg.kg-1 de cetamina nebulizada (Grupo C-N2). O desfecho primário foi o consumo total de analgésicos de resgate nas primeiras 24 horas de pós-operatório. Resultados O tempo médio para a primeira solicitação de analgésicos de resgate foi prolongado nos grupos C-N1 (400,9 ± 60,5 min, IC 95% 375,9-425,87) e C-N2 (455,5 ± 44,6 min, IC 95% 437,1-473,9) em comparação com o Grupo C-IV (318,5 ± 86,1 min, IC 95% 282,9-354,1) e o Grupo C (68,3 ± 21,9 min, IC 95% 59,5-77,1; p < 0,001), com uma diferença significativa entre os grupos C-N1 e C-N2 (p < 0,001). O consumo total de paracetamol IV nas primeiras 24 horas de pós-operatório foi reduzido no Grupo C-IV (672,6 ± 272,8 mg, IC 95% 559,9-785,2), Grupo C-N1 (715,6 ± 103,2 mg, IC 95% 590,4-840,8) e Grupo C-N2 (696,6 ± 133,3 mg, IC 95% 558,8-834,4) em comparação com o Grupo C (1153,8 ± 312,4 mg, IC 95% 1024,8-1282,8; p < 0,001). Não houve diferença entre os grupos de cetamina intravenosa e nebulizada (p = 0,312). Os pacientes dos grupos de cetamina intravenosa e nebulizada apresentaram escores VRS pós-operatórios menores, em comparação com o Grupo C (p < 0,001), sem diferenças entre os grupos C-IV, C-N1 ou C-N2 e sem efeitos adversos significativos. Conclusão A administração preventiva de cetamina nebulizada foi eficaz no alívio da dor pós-amigdalectomia. Cetamina nebulizada pode ser considerada como uma via alternativa eficaz à cetamina IV.

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Resumen: Introducción: El dolor faríngeo postoperatorio es una complicación frecuente posterior a la intubación endotraqueal, caracterizado por odinofagia. Objetivo: Comparar ketamina nebulizada preoperatoria contra placebo para la disminución del dolor faríngeo postoperatorio en cirugía electiva bajo anestesia general. Material y métodos: Estudio experimental prospectivo, aleatorizado, doble ciego, realizado de febrero a julio del 2016. Dos grupos de pacientes aleatorizados: grupo K: ketamina nebulizada (50 mg: 1 mL de ketamina + 2 mL de solución salina 0.9%); grupo P: placebo (nebulización de 3 mL solución salina 0.9%). Se evaluaron signos vitales así como síntomas e intensidad del dolor faríngeo postoperatorio de acuerdo con la escala numérica análoga a la hora 1 y a la hora 4. Resultados: El uso de ketamina nebulizada no representa una ventaja estadísticamente significativa con relación al placebo para el dolor faríngeo postoperatorio. La incidencia de éste en nuestro estudio fue de 59.29%. Conclusiones: Se necesitan más estudios con ketamina nebulizada en vía aérea difícil en la población mexicana, así como una mayor muestra para poder determinar el estándar de oro para el tratamiento del dolor faríngeo postoperatorio.

Abstract: Introduction: The postoperative sore throat is a frequent complication, characterized by odynophagia after endotracheal intubation. Objective: To compare nebulized ketamine in the preoperative period against nebulized placebo for the reduction of the postoperative sore throat on elective surgery under general anesthesia. Material and methods: We performed an experimental, prospective, randomized, double blind study; conducted from February to July 2016. Patients were randomly assigned into two groups: group K: preoperative nebulized ketamine (50 mg: 1 mL of ketamine + 2 mL of saline solution 0.9%) against group P: placebo (nebulization of 3 mL saline solution 0.9%). We collected vital signs as well as symptoms and intensity of postoperative sore throat according to the analog numeric scale at the first and forth postoperative hours. Results: The use of nebulized ketamine does not represent a statistically significant difference compared to placebo for postoperative sore throat. The incidence of postoperative sore throat in our study was of 59.29%. Conclusions: We need further studies of nebulized ketamine in the Mexican population, as well as a larger study to determine the gold standard for the treatment of POST.

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Aerosolized amikacin reaches high concentrations in lung fluids, which are well above the minimum inhibitory concentrations (MICs) of resistant strains of Pseudomonas aeruginosa. However, P. aeruginosa can gain resistance to amikacin through different cumulative mechanisms; amikacin MICs are seldom reported beyond values of 1,000 µg/ml, as tested in clinical microbiology assays. To assess how high amikacin MICs can be reached by graded exposure, four amikacin-resistant P. aeruginosa isolates were grown in a 4-step increased exposure to amikacin; derivative strains were further characterized by measuring their comparative growth rate, biofilm-forming ability, and susceptibility to other antibiotics. In addition, the mechanism underlying the MIC increase was assessed phenotypically, using a set of 12 aminoglycoside disks, and measuring the effect of Phe-Arg-ß-naphthylamide, an efflux pump inhibitor. Graded exposure to amikacin increased MICs of resistant strains up to 10,000-20,000 µg/ml, without apparent fitness cost, and having variable consequences on their biofilm-forming ability, and on their susceptibility to other antibiotics. Decreased permeability may have contributed to hyper-resistance, although evidence was inconclusive and variable between strains. Amikacin-resistant P. aeruginosa is able to gain in vitro hyper-resistance with minimal changes in the specific phenotypes that were tested; the ability to achieve high-level amikacin (AMK) resistance may confound the clinical utility of this aerosolized AMK, but clinical data would be required to assess this.

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Objetivo: Evaluar la eficacia de salbutamol y dexametasona nebulizados comparados con salbutamol solo en pacientes con bronquiolitis aguda. Material y métodos: Estudio clínico controlado, aleatorizado, en pacientes de 1 a 18 meses de edad con diagnóstico de bronquiolitis aguda y evolución menor de tres días. Se asignaron dos grupos: 1) salbutamol (n = 24) o 2) salbutamol más dexametasona (n = 25) administrado por micronebulizaciones cada cuatro horas por 24 horas. Se midieron las frecuencias cardiaca y respiratoria, la gravedad del cuadro mediante el Respiratory Distress Assigment Index, el Silvermann-Andersen, saturación de O2 y tiempo de desaparición de la dificultad respiratoria y frecuencia de altas en 24 horas. Resultados: No se encontraron diferencias significativas entre los grupos de estudio, excepto en la frecuencia de altas hospitalarias en las primeras 24 horas, 75 vs 96 % p < 0.04 respectivamente. Conclusiones: La aplicación de salbutamol más dexametasona es más rápida para controlar la dificultad respiratoria en niños con bronquiolitis aguda en comparación con la aplicación de salbutamol solo.

OBJECTIVE: Asess the efficacy of nebulized salbutamol and dexamethasone compared with nebulized salbutamol, in patients with bronchiolitis. MATERIAL AND METHODS: A blinded clinical trial was performed with 49 patients between 1-18 months diagnosed with bronchiolitis with three days or less of disease evolution. Participant's parents signed an informed consent and patients did not receive prior medication. Patients were randomly assigned to two groups: nebulized salbutamol or salbutamol plus dexamethasone, which they received every four hours during twenty-four hours. We measured heart and respiratory rate; respiratory distress index, oxygen saturation, and Silverman Andersen scores. RESULTS: No significant differences were found between groups for treatment response; but the frequency of hospital release at 24 hrs was significant among groups; 75 vs 96 % respectively (p = 0.04). CONCLUSIONS: The administration of salbutamol plus dexamethasone is more effective in the control of respiratory distress in children with bronchiolitis compared with the use of salbutamol alone.

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