Bioavailability of vitamin B using a small-volume nebulizer ophthalmic drug delivery system

BACKGROUND: To determine the intraocular bioavailability of a novel embodiment for vitamin B(12) delivered to the ocular surface by a piezo-electric ultrasonic nebulizer. METHODS: The semisolid embodiment contained 0.02% (w/w) vitamin B(12) in 1 g of ointment, which was immiscible and insoluble in 5 mL sterilized warm water. To confirm in vitro functionality, nebulized mist particles of the embodiment were collected and analysed for vitamin B(12) content. The in vivo arm of the study was designed as randomization of 23 patients who were scheduled to undergo cataract surgery in hospital. Fourteen patients were treated with nebulized vitamin B(12), five patients had one drop of 0.02% vitamin B(12) instilled in the conjunctival cul de sac, and four control patients had no medication. Twelve hours after the vitamin was delivered, the patients underwent the cataract procedure and a sample of aqueous humour was collected from each. High performance liquid chromatography was used for detection of vitamin B(12) in all samples. RESULTS: The in vitro analysis of mist particles showed increasing concentrations of vitamin B(12). In the patient tests, analysis of the aqueous humour samples showed that none of the controls or those receiving eye drops had detectable vitamin B(12) in the aqueous humour. However, 4 of 14 in the nebulizer group had vitamin B(12) detected in the aqueous humour in the amount of 10(-7) mol. CONCLUSIONS: The small-volume nebulizer system might provide another method of ophthalmic drug delivery.     

Salbutamol treatment of acute severe asthma in the ED: MDI versus hand-held nebulizer

The objectives of this study were to compare the efficacy of salbutamol delivered by either metered-dose inhaler plus spacer (MDI-spacer) or by wet nebulization (NEB), and to determine the relationships between physiologic responses and plasma salbutamol concentrations. Asthmatic patients presenting to the emergency department (ED) with acute severe asthma (forced expiratory volume in the first second [FEV₁] less than 50% of predicted) were enrolled in a randomized, double-blind, parallel-group study. The MDI-spacer group received salbutamol, delivered via MDI into a spacer device, in four puffs actuated in rapid succession at 10-minute intervals (2.4 mg/h). The NEB group was treated with nebulized salbutamol, 1.5 mg, via nebulizer at 15-minute intervals (6 mg/h). Doses were calculated on the basis of the percentage of total dose that reaches the lower airway with both methods. The protocol involved 3 hours of this treatment. Mean peak expiratory flow rate (PEFR) and FEV₁ improved significantly over baseline values for both groups (P = .01). However, there were no significant differences between both groups for PEFR and FEV₁ at any point studied. The examination of the relationships between cumulative dose of salbutamol and change in FEV₁ showed a significant linear relationship (P = .01) for both methods (MDI r = .97; NEB r = .97). The regression equations showed that for every 1 mg of salbutamol by MDI-spacer, 2.5 mg are needed from nebulization to have equal therapeutic response. At the end of treatment, the salbutamol plasma levels were 10.1 ± 1.6 ng/ml for the MDI-spacer group and 14.4 ± 2.3 ng/ml for the NEB group (P = .0003). Both groups showed a nonsignificant heart rate decrease. A significant group-by-time interaction means that differences between groups increased with time (P = .04). Additionally, the NEB group presented a higher incidence of tremor (P = .03) and anxiety (P = .04), reflecting larger systemic absorption of salbutamol. These data indicate that when doses used are calculated on the basis of the percentage of total drug that reaches the lower airway, there was equivalent bronchodilatation after salbutamol administered by either MDI-spacer or nebulization in patients with acute severe asthma. However, nebulizer therapy produced greater side effects related to the increase in salbutamol absorption and higher plasma level.     

Efficacy of bronchodilators administered by nebulizers versus spacer devices in infants with acute wheezing

The aim of this study was to compare the response of infants with acute wheezing to treatments with inhaled terbutaline when administered by nebulizer or by metered-dose inhaler and spacer device (MDI-spacer). Thirty-four infants between the ages of 1 and 24 months who were seen in our emergency department for acute wheezing were studied in a double-blind, randomized trial. The participants received two treatments of terbutaline at 20-min intervals, either by a nebulizer (2 mg/dose in 2.8 mL of 0.9% saline solution) or by an MDI-spacer device (0.5 mg/dose). The outcome measure was a clinical score, based on respiratory rate, degree of wheezing, retractions, degree of cyanosis, color, and pulse oximetry data measured before treatment, 20 min after the first treatment, and again 20 min after the second treatment. There was no difference in the rate of improvement in the clinical score between infants who received terbutaline by nebulizer and those who received it by MDI-spacer. We conclude that MDI-spacers and nebulizers are equally effective means of delivering beta-2 agonists to infants and small children with acute wheezing. Pediatr Pulmonol. 1998; 26:344–348. © 1998 Wiley-Liss, Inc.     

Nebulization of Fluids of Different Physicochemical Properties with Air-Jet and Ultrasonic Nebulizers

Purpose. Empirical formulae relate the mean size of primary droplets from jet and ultrasonic nebulizers to a fluid's physicochemical properties. Although the size selective filtering effects of baffling and evaporation may modify the secondary aerosol produced, this research sought to evaluate whether viscosity and surface tension of nebulized fluids influenced the aerosol's size and output characteristics. Methods. Fluid systems of different surface tension and viscosity (glycerol and propylene glycol solutions [10–50% (v/v)] and a range of silicone fluids [200/0.65 cs– l00cs]) were nebulized in three jet and two ultrasonic nebulizers. Secondary aerosol characteristics were measured with a Malvern 2600C laser diffraction sizer and the nebulization times, residual volumes and percentage outputs were determined. Results. While the droplet size appeared to be inversely proportional to viscosity for jet nebulizers, it was directly proportional to viscosity for ultrasonic nebulizers. Although fluid systems with lower surface tensions generally produced slightly smaller MMDs, the relationship between surface tension and droplet size was complex. The more viscous fluids required longer nebulization times and were associated with increased residual amounts (lower outputs). The ultrasonic nebulizers did not effectively, and were on occasion unable to, nebulize the more viscous fluids. Conclusions. It follows that there are cut-off values for viscosity and/or surface tension above or below which ultrasonic devices fail to operate. Moreover, jet nebulizers generated an aerosol with an optimum respirable output from median-viscosity fluids.     

Comparison of bronchodilator administration with vibrating mesh nebulizer and standard jet nebulizer in the emergency department

Introduction

Projects comparing bronchodilator response by aerosol devices in the ED are limited. Evidence suggests that the vibrating mesh nebulizer (VMN) provides 5-fold greater aerosol delivery to the lung as compared to a jet nebulizer (JN). The aim of this project was to evaluate a new nebulizer deployed in an Emergency Department.

Nebulized Ketamine Used for Pain Management of Orthopedic Trauma

BackgroundKetamine is a noncompetitive N-methyl-D-aspartate/glutamate receptor complex antagonist that decreases pain by diminishing central sensitization and hyperalgesia. When administered via i.v. (push-dose, short infusion, or continuous infusion) or intranasal routes, ketamine has shown to be effective in patients with acute traumatic pain. However, when i.v. access is not attainable or readily available, the inhalation route of ketamine administration via breath-actuated nebulizer (BAN) provides a noninvasive and titratable method of analgesic delivery. The use of nebulized ketamine has been studied in areas of postoperative management of sore throat and acute traumatic musculoskeletal and abdominal pain. To our knowledge, this is the first case series describing the use of nebulized ketamine for analgesia and orthopedic reduction.Case SeriesWe describe 4 patients who presented to the emergency department with acute traumatic painful conditions (one patellar dislocation, one shoulder dislocation, and two forearm fractures) and received nebulized ketamine for management of their pain.Why Should an Emergency Physician Be Aware of This?Administration of nebulized ketamine via BAN can be used as analgesic control for musculoskeletal trauma, as it can be administrated to patients with difficult i.v. access, has a rapid onset of analgesic effects with minimal side effects, and remains opioid-sparing.     

雾化吸入硝酸甘油对慢性肺心病血流动力学的影响

目的 观察雾化吸入硝酸甘油对慢性肺心病血流动力学的影响.方法 将60例符合条件的慢性肺心病住院患者随机分为治疗组和对照组.对照组给予常规治疗,治疗组在常规治疗的基础上加用雾化吸入硝酸甘油,3d后观察二组的临床疗效.结果 治疗组显效率73.3%,总有效率为90.0%;对照组显效率为46.7%,总有效率为67.2%,治疗后二组疗效对比,显效率和总有效率差异均有统计学意义(P＜.05).雾化吸入硝酸甘油10 min、60 mim、1 d、2 d和3 d右室射血前期(RPEP)/加速时间(AT)、肺动脉平均压(PAMP)均较吸入前基础值明显下降(P＜.05).而HR、平均动脉压(MAP)、肺动脉峰值血流速度(PA)及雾化吸入硝酸甘油后与吸入前基础值相比均无明显变化(P＜0..05).结论 雾化吸入硝酸甘油可以降低慢性肺心病肺动脉高压,改善肺动脉高压患者肺循环的血流动力学,而对体循环无明显影响.     

A review of the technical aspects of drug nebulization

Nebulizers are widely used for the inhalation of drug solutions in a variety of respiratory diseases. The efficacy of nebulizer therapy is influenced by a great number of factors, including the design of the device and the characteristics of the drug solution. Incorrect cleaning, maintenance and disinfection procedures may change the nebulizer performance in time, whereas patient factors can influence the lung deposition of the generated aerosol. In this review the technical aspects of nebulization of drug solutions will be discussed. Two main parameters are generally used to evaluate the performance of nebulizers: the droplet size distribution of the aerosol and the drug output rate. The droplet size distribution and the drug output rate are basically determined by the design and user conditions of the nebulizer. A higher gas flow of the compressor in a jet nebulizer or a higher vibration frequency of the piezo electric crystal in an ultrasonic nebulizer, decreases the droplet size. The choice of the type of nebulizer for nebulization of a certain drug solution may initially be based on laboratory evaluation. The major part of the mass or volume distribution should preferably correspond with aerodynamic particle diameters in the range of 1 to 5 micrometer. The intended drug output must be realized within a reasonable nebulization time (less than 30 min). From the drug output only a minor fraction will be deposited in the lung. The relation between in vitro and in vivo deposition is only partly understood and to date it has not been possible to predict drug delivery only from in vitro studies on nebulizers. Therefore, studies in patients should be performed before a drug solution for nebulization can be recommended for clinical practice. The mechanical properties of nebulizers are likely to change during use. An average utilization time of nebulizers is not available. Therefore, the performance of nebulizers should be checked periodically. Patient compliance in nebulizer therapy is relatively low. This is partly due to the fact that, at present, drug solutions for nebulizers cannot be administered efficiently within a short period of time. More efficient systems should be developed. If possible, nebulizers should be substituted to more efficient systems, e.g. dry powder inhalers or metered dose inhalers.