Search

Background: Transient tachypnea of the newborn [TTN] is a common physiologic lung disorder. Stimulation of β-adrenergic receptors could alleviate the condition. Aim of the work: The study was undertaken to assess the efficacy and safety of inhaled salbutamol in reduction of TTN, oxygen treatment and hospitalization. Patients and Methods:This clinical study included 150 [50 control group, 50 single dose of salbutamol and 50 double-doses of salbutamol] infants between 35th-39th week's gestation. Inhaled salbutamol was given and comparison between the three groups was carried out. Results: Treatable and control groups were comparable as regard neonatal and maternal characteristics. Heart rate was significantly increased in group B when compared to control group half and one hour after treatment. In addition, respiratory rate was significantly increase in group B when compared to group A at half hour after treatment and continued till 8 hours after treatment. The TTN score after treatment was significantly lower in group B when compared to group A at one hour after nebulized salbutamol and continued till 8 hours. Furthermore, time before initiation of feeding was significantly reduced in group B when compared to group A [26.72[±3.68] vs [39.66[±4.7] and also there was significant reduction of hospitalization days in group B when compared to group A [3.78 [±1.25] vs [7.36[±1.28]. Conclusion: Inhalational salbutamol reduced duration of supplemental oxygen therapy, the duration of hospitalization and time before initiation of feeding, and no adverse effects were reported. Thus, inhaled salbutamol seems to be effective and safe in TTN.

Background: This study was aimed to compare the effect of nebulized fentanyl versus intravenous fentanyl for postoperative analgesia after unilateral femur interlock surgery. Patients and Methods: A total of sixty patients scheduled for unilateral femur interlock surgery under subarachnoid block were enrolled in the study and were randomly divided into two groups. Group I included thirty patients who received 2 μg/kg of fentanyl intravenously, and Group N included thirty patients who received 4 μg/kg of fentanyl nebulization using a standard venturi mask. In the postoperative period, whenever the Visual Analog Scale ≥4, patients received the analgesic corresponding to their respective groups. The data obtained were statistically analyzed using IBM SPSS software. Results: There was no significant difference in the demographic characteristics, duration of surgery, the number of patients who required rescue analgesia, and the onset of analgesia in Group N in comparison with Group I. The duration of analgesia was significantly longer in Group N in comparison to Group I. In Group I, the rise in Ramsay sedation score was faster and peaked at 5 min. In Group N, however, it was lesser than that of Group I. Side effects in Group N were significantly lesser compared to Group I. Conclusion: Nebulization with fentanyl is a good alternative to intravenous fentanyl for adequate postoperative pain relief with fewer side effects.

Background Aerosolized antibiotic administration offers the theoretical advantages of achieving high drug concentrations at the infection site together with lower systemic absorption. This study aims to compare the effect of combining nebulized amikacin with intravenous amikacin to the effect of the usual intravenous route alone in the treatment of patients with ventilator-associated pneumonia and its impact on the duration of mechanical ventilation, laboratory, and clinical picture of the patients. Results This study was carried out on 64 mechanically ventilated patients with Gram-negative VAP. The patients were divided into 2 groups. Group A included 32 patients treated with nebulized amikacin plus IV amikacin, and group B included 32 patients treated with IV amikacin alone. The duration of treatment for both groups was 8 days with a daily assessment of Clinical Pulmonary Infection Score (CPIS) and monitoring of clinical and laboratory parameters. Sputum cultures were obtained thereafter. In our study, the CPIS score and overall ICU mortality were less in the nebulized than in the IV group but the difference failed to be statistically significant. Increase of oxygenation level (Pao2/Fio2 ratio), organism clearance, decrease in serum creatinine level, duration of mechanical ventilation, and length of ICU stay were significantly different in favor of group A than group B. Conclusion Nebulized and IV amikacin offered better oxygenation, organism clearance, less nephrotoxicity, and less duration of mechanical ventilation and ICU stay than the IV group. Combined and IV routes were comparable regarding the decrease in CPIS score and ICU mortality with no significant difference between them. However, we prefer to use the combined regimen for the mentioned reasons. Further large-scale studies are required to confirm these findings and to establish a definite conclusion.

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 =

Background Revefenacin (TD-4208) is a potent, lung-selective, long-acting muscarinic antagonist currently in development as a once-daily nebulized therapy for chronic obstructive pulmonary disease (COPD). We evaluated the pharmacodynamics (bronchodilator activity), pharmacokinetics (PK) and safety of single- and multiple-dose administrations of revefenacin in two clinical trials (Study 0059 and Study 0091) in patients with moderate to severe COPD. Methods In Study 0059, 32 patients were randomized to receive a single dose of revefenacin (350 or 700 μg), active control ipratropium (500 μg) or placebo inhalation solution administered via standard jet nebulizer in a double-blind, crossover fashion. In Study 0091, 59 patients were randomized to receive once-daily inhalations of revefenacin (22, 44, 88, 175, 350 or 700 μg) or placebo for 7 days in a double-blind, incomplete block, five-way crossover design. The primary efficacy endpoint was change from baseline in peak (0–6 h) forced expiratory volume in 1 s (FEV1) in Study 0059, and trough FEV1 after the final dose (Day 7) in Study 0091. In both studies, secondary endpoints included area under the FEV1-time curve (FEV1 AUC) values from time 12–24 h post dose and FEV1 AUC values from time zero to 24 h post dose. Results Revefenacin demonstrated a rapid onset and sustained duration of bronchodilator action in both studies. In Study 0059, mean peak FEV1 was significantly higher (p < 0.001) for revefenacin and ipratropium compared to placebo, with differences of 176.8 mL for 350 μg revefenacin, 162.2 mL for 700 μg revefenacin and 190.6 mL for ipratropium. In Study 0091, mean trough FEV1 on Day 7 was significantly higher (p < 0.006) for all revefenacin doses compared to placebo, with differences ranging from 53.5 mL (22 μg dose) to 114.2 mL (175 μg dose). The results for the other spirometry endpoints were consistent with the primary endpoint for each study, demonstrating that the bronchodilator effect of revefenacin lasted more than 24 h following nebulized administration. Revefenacin was rapidly absorbed and extensively metabolized, followed by a slow apparent terminal elimination and minimal accumulation with repeated dosing. In both studies, adverse events were generally mild and occurred with similar frequencies in all groups, with no indication of significant systemic anti-muscarinic activity at any dose. Conclusions Following single or multiple nebulized-dose administration in patients with COPD, revefenacin demonstrates a rapid onset and sustained duration of bronchodilator effect over 24 h following once-daily administration, with a PK profile that is commensurate with low systemic exposure.

Background Asthma is characterized by airways narrowing and airflow limitation. The conventional therapy for asthma exacerbation is usually efficient but sometimes patients not respond to it, consequently; other additive drugs may be used as magnesium sulfate(MgSO 4 ) either intravenously or by nebulization. Objective To compare the bronchodilator effect of MgSO 4 via intravenous injection and nebulization in controlling asthma exacerbation. Methods 40 patients with asthma exacerbation were equally and randomly enrolled in two groups. One group received nebulized MgSO 4 (A), and the other group received intravenous MgSO 4 (B). Results Improvement was higher in group B than in group A but without significant change in PEFR also there was no high significant difference in the two group parameters after MgSO 4 treatment. Complications were few and manageable in both groups. Conclusion Intravenous MgSO 4 is effective affordable and cheap drug for asthma exacerbation management with good response while nebulized MgSO 4 didn’t give the aimed response in these patients.

Background Intravenous morphine titration (IVMT) is the French gold standard for opioid treatment in the emergency department (ED). Nebulized morphine titration (NMT) may represent an alternative without venous access, but it has not been adequately studied in adults. We test the hypothesis that NMT is at least as effective as IVMT to initially manage severe acute pain in the ED. Methods/design We designed a multicenter (10 French EDs), single-blind, randomized and controlled trial. Adults between 18 and 75 years with visual analog scale (VAS) ≥ 70/100 or numeric rating scale (NRS) ≥ 7/10 will be enrolled. We will randomize 850 patients into two groups to compare two routes of MT as long as VAS > 30 or NRS > 3. In group A (425), patients will receive an initial NMT for 5–25 min associated with titration of an intravenously (IV) administered placebo of physiologic serum (PS). In group B (425), patients will receive IVMT plus nebulized PS placebo. NMT is defined as a minimum of 1 and a maximum of 3 5-min nebulized boluses of 10 mg or 15 mg (weight ≥ 60 kg), at 10-min fixed intervals. IVMT is defined as a minimum of 1 and a maximum of 6 boluses of 2 mg or 3 mg (weight ≥ 60 kg), at 5-min fixed intervals. Nebulized placebo titration will be performed every 10 min. IV titration of PS will be performed every 5 min. In both groups, after 25 min, if VAS > 30/100 or NRS > 3/10, routine IVMT will be continued until pain relief. Pain severity, vital signs, bronchospasm, and Ramsay score will be recorded every 5 min. The primary outcome is the rate of relief obtained 1 h from the start of drug administration. Complete pain relief in both groups will be compared with a non-inferiority design. Secondary outcomes are pain relief at 30 min (the end of NMT) and at 2 h and median pain relief. We will compare final doses, and study the feasibility and tolerance of NMT (protocol deviations, respiratory or hemodynamic depression, sedation, and minor vegetative side effects). Co-analgesia will be recorded. Discharge criteria from the ED and hospital are defined. Discussion This trial is the first multicenter randomized and controlled NMT protocol for severe pain in the ED using the titration concept. We propose an original approach of combined titration with an endpoint at 1 h and a non-inferiority design. Trial registration ClinicalTrials.gov, NCT03257319. Registered on 22 August 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3326-3) contains supplementary material, which is available to authorized users.

Revefenacin is a novel once‐daily, lung‐selective, long‐acting muscarinic antagonist developed as a nebulized inhalation solution for the maintenance treatment of chronic obstructive pulmonary disease. In a randomized, 4‐way crossover study, healthy subjects received a single inhaled dose of revefenacin 175 µg (therapeutic dose), revefenacin 700 µg (supratherapeutic dose), and placebo via standard jet nebulizer, and a single oral dose of moxifloxacin 400 mg (open‐label) in separate treatment periods. Electrocardiograms were recorded, and pharmacokinetic samples were collected serially after dosing. The primary end point was the placebo‐corrected change from baseline QT interval corrected for heart rate using Fridericia's formula, analyzed at each postdose time. Concentration‐QTc modeling was also performed. Following administration of revefenacin 175 and 700 µg, placebo‐corrected change from baseline QTcF (ΔΔQTcF) values were close to 0 at all times, with the largest mean ΔΔQTcF of 1.0 millisecond (95% confidence interval [CI], −1.2 to 3.1 milliseconds) 8 hours postdose and 1.0 millisecond (95%CI, −1.1 to 3.1 milliseconds) 1 hour postdose after inhalation of revefenacin 175 and 700 µg, respectively. Revefenacin did not have a clinically meaningful effect on heart rate (within ±5 beats per minute of placebo), or PR and QRS intervals (within ±3 and ±1 milliseconds of placebo, respectively). Using concentration‐QTc modeling, an effect of revefenacin > 10 milliseconds can be excluded within the observed plasma concentration range of up to ≈3 ng/mL. Both doses of revefenacin were well tolerated. These results demonstrate that revefenacin does not prolong the QT interval.

Introduction Gastric overdistension by mask ventilation during induction of anesthesia in congenital diaphragmatic hernia (CDH) repair may worsen hypoxemia. Topical airway anesthesia may improve the intubating conditions during sevoflurane induction without muscle relaxation. The present study was designed to evaluate the effect of nebulized lidocaine and fentanyl on the intubating conditions without muscle relaxation during sevoflurane induction of anesthesia in infants undergoing CDH repair. The secondary aim was studying hemodynamic changes during induction. Patients and methods Forty patients scheduled for (CDH) repair were randomly selected and blindly categorized to the following: Nebulizer group: Nebulized solution of 4 mg kg −1 lidocaine 1% plus 2 μg kg −1 fentanyl, Control group: Nebulized solution of comparable volume/weight normal saline 0.9%. Nebulizer of either solution was applied 15 min before sevoflurane induction. Results Heart rate (HR) and mean arterial blood pressure (mABP) statistically significantly increased in the control group following intubation and for 2 min regarding HR and for 5 min regarding mABP in comparison with the base line and relative to the nebulizer group. There was a statistical significant improvement regarding the intubation conditions in the nebulizer group relative to the control group ( p ⩽ 0.001). The same was noticed regarding the intubation time and the number of intubation attempts ( p ⩽ 0.001). Conclusions Premedication of infants undergoing CDH repair with nebulized solution containing 4 mg kg − 1 lidocaine 1% plus 2 μg kg − 1 fentanyl improves the intubating conditions under inhalational sevoflurane induction without muscle relaxation. The studied combination can suppress patients’ hemodynamic changes to intubation.

Background and aim. In the last decade a significant increase of nebulized medication usage has been documented in Romania. Authors are aiming to describe parental and physician’s change of perspective regarding nebulized medication in the new era of online communication and education. Material and methods. Two different questionnaires were posted in a large and representative group (more than 60,000 followers) of Romanian parents and physicians, Virtual Children’s Hospital („Spitalul Virtual de Copii”). Results. More than 4,000 answers were submitted. 94.4% responders confirmed using at least once wetnebulized medication in children. A particular aspect documented was dexamethasone off-label usage via nebulizer in 67.8% children. Additional 7% of responders confirmed that they received an indication to nebulize a normal saline suspension with dexamethasone phosphate for parenteral usage, but they didn’t follow the indication and used an approved treatment. Conclusions. Upon our knowledge this is the first large study on nebulized dexamethasone in Romanian literature. 95% of Romanian children receive nebulized medication. Nebulizer is regarded by parents as a simple and friendly tool that can solve virtually all issues related to airway diseases in our country. 75% of children that received nebulized medication had a prescription for off-label use of dexamethasone.

There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation of amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships of these drugs have not been fully characterized. The aim of this study was to describe the individual and combined antibacterial effects of simulated epithelial lining fluid exposures of aerosolized amikacin and fosfomycin against resistant clinical isolates of Pseudomonas aeruginosa (MICs of 16 mg/liter and 64 mg/liter) and Klebsiella pneumoniae (MICs of 2 mg/liter and 64 mg/liter) using a dynamic hollow-fiber infection model over 7 days. Targeted peak concentrations of 300 mg/liter amikacin and/or 1,200 mg/liter fosfomycin as a 12-hourly dosing regimens were used. Quantitative cultures were performed to describe changes in concentrations of the total and resistant bacterial populations. The targeted starting inoculum was 10 8 CFU/ml for both strains. We observed that neither amikacin nor fosfomycin monotherapy was bactericidal against P. aeruginosa while both were associated with rapid amplification of resistant P. aeruginosa strains (about 10 8 to 10 9 CFU/ml within 24 to 48 h). For K. pneumoniae , amikacin but not fosfomycin was bactericidal. When both drugs were combined, a rapid killing was observed for P. aeruginosa and K. pneumoniae (6-log kill within 24 h). Furthermore, the combination of amikacin and fosfomycin effectively suppressed growth of resistant strains of P. aeruginosa and K. pneumoniae . In conclusion, the combination of amikacin and fosfomycin was effective at maximizing bacterial killing and suppressing emergence of resistance against these clinical isolates.

Background: Ventilator-associated pneumonia (VAP) due to multidrug-resistant organisms (MDROs) is associated with a significant mortality in the Intensive Care Unit (ICU). The aim of this study was to compare the efficacy and safety of extended infusion of meropenem and nebulized amikacin on VAP caused by Gram-negative MDRO versus intravenous (IV) meropenem and amikacin alone. Methodology: A randomized nonblinded controlled trial was performed on ninety patients with VAP. Patients were randomized into three equal groups: Group I received IV amikacin 20 mg/kg/24 h and meropenem 2 g over 30 min/8 h. Group II received the same as Group I in addition to nebulized amikacin 25 mg/kg/day every 8 h. Group III received IV amikacin 20 mg/kg/24 h, nebulized amikacin 25 mg/kg/day every 8 h, and meropenem 2 g diluted in 240 ml normal saline over 3 h/8 h. The primary outcome was the clinical outcome of VAP. Secondary outcomes were microbiological outcome, VAP-related mortality, duration of MV, ICU stay, and nephrotoxicity. Results: Group II and Group III compared to Group I showed higher incidence of clinical cure (53.33% in Group II and 66.67% in Group III vs. 26.67% in Group I, P = 0.007). Group II compared to Group I showed significant reduction in ventilator days (5.32 ± 1.86 vs. 7.3 ± 2.1 days, respectively, P < 0.001) and reduction in ICU days (11.87 ± 2.6 vs. 15.3 ± 3.1 days, respectively, P < 0.001). Group III compared to Group II showed significant reduction in ventilator days (4.22 ± 1.32 vs. 5.32 ± 1.86, respectively, P = 0.011) and highly significant reduction in ICU days (9.21 ± 1.17 vs. 11.87 ± 2.6, respectively, P < 0.001). All groups were comparable as regards nephrotoxicity or mortality. Conclusions: Adding nebulized amikacin to systemic antibiotics in patients with VAP caused by Gram-negative MDRO may offer efficacy benefits, and the use of extended infusions of meropenem could improve the clinical outcomes in critically ill populations.

β2-agonists have questionable symptomatic effect in infants with acute bronchiolitis, whereas inhaled, nebulized racemic adrenaline, commonly used in Norway, appears (clinically) to be effective. Limited lung function observations during acute bronchiolitis exists, and less for assessing possible effects inhaled adrenaline.In this preliminary study, tidal flow-volume loops were measured in 16 infants with acute bronchiolitis and seven healthy controls (mean age 7·9 and 4·4 months, respectively), with repeated measurements 15 min after inhaled nebulized racemic adrenaline (4 mg diluted in 2 ml saline) in nine bronchiolitis patients.The ratio of time to reach peak tidal expiratory flow to total expiratory time (tPTEF/tE) was significantly reduced in children with acute bronchiolitis (mean, 95% CI) (0·08, 0·05–0·10) compared to controls (0·31, 0·18–0·43), with significant improvement after inhaled racemic adrenaline 0·19 (0·13–0·25), parallel with significant clinical improvement.Lung function (tPTEF/tE) was reduced in infants with acute bronchiolitis and improved significantly after inhaled racemic adrenaline. Inhaled racemic adrenaline is potentially an important alternative for treating infants with acute bronchiolitis.

Background: The efficacy of steroid administration in the prevention of postextubation complications in critical care remains controversial. The purpose of this study was to determine whether administration of nebulized budesonide in critically ill patients reduces the occurrence of postextubation airway complications. Materials and Methods: This was a prospective, randomized, double-blind, placebo-controlled study.We prospectively followed up 70 adult patients in the intensive care unit who were intubated for more than 48 h. Patients received either nebulized budesonide (1 mg every 12 h; n = 35) or placebo (normal saline; n = 35) until 48 h after extubation. Then, the postextubation complications were assessed and recorded within 48 h of extubation. Results: The incidence of respiratory distress was lower in budesonide group (8.6% vs. 31.4%, P = 0.017). Reintubation with mechanical support was necessary in 8.6% (3.35) of patients in the budesonide group and 31.4% (11.35) of patients in the placebo group (P = 0.017). Conclusion: Nebulized budesonide after extubation is effective in reducing the incidence of reintubation and respiratory distress in adult patients.

Repeated bouts of acute and chronic lung infections are responsible for progressive pulmonary function decline in individuals with cystic fibrosis (CF), ultimately leading to respiratory failure and death. Pseudomonas aeruginosa is the archetypical CF pathogen, causes chronic infection in 70% of individuals, and is associated with an accelerated clinical decline. The management of P. aeruginosa in CF has been revolutionized with the development and widespread use of inhaled antibiotics. Aerosol delivery of antimicrobial compounds in CF enables extremely high concentrations of antibiotics to be reached directly at the site of infection potentially overcoming adaptive resistance and avoiding the potential for cumulative systemic toxicities. Tobramycin inhalation powder (TIP) represents the first dry powder inhaled (DPI) antibiotic available for use in CF. DPIs are notable for a markedly reduced time for administration, ease of portability, and increased compliance. TIP has been developed as a therapeutic alternative to tobramycin inhalation solution (TIS), the standard of care for the past 20 years within CF. Relative to TIS 300 mg nebulized twice daily in on-and-off cycles of 28 days duration, TIP 112 mg twice daily via the T-326 inhaler administered on the same schedule is associated with marked time savings, increased patient satisfaction, and comparable clinical end points. TIP represents an innovative treatment strategy for those individuals with CF and holds the promise of increased patient compliance and thus the potential for improved clinical outcomes.

Objective: To estimate the efficacy and safety of nebulized tobramycin (NT) as an adjunct to systemic antibiotics in the treatment of severe nosocomial pneumonia (NP). Methods: 25 mechanically ventilated patients (out of 150 screened) were enrolled in the current observational single-center study. They were randomized to receive either NT (300 mg, BID; group 1, n=15) as an adjunct to systemic antibiotics or for a correction of the regimen of systemic antibiotics (group 2, n=10). The primary outcome measure was resolution of NP and acute respiratory insufficiency. The CPIS, signs of systemic inflammatory response syndrome (SIRS) and oxygenation index were used as objective indicators of the clinical progress. Results: The following signs of NT efficacy were detected in 87% of group 1 patients: a decrease of SIRS and CPIS scores within (2.3±1.2) d of NT therapy (P