In vitro study and semiempirical model for aerosol delivery control during mechanical ventilation

The object of this study was to evaluate in vitro the influence of various ventilatory parameters on the delivery of synchronized nebulization of terbutaline during mechanical ventilation and to determine a semiempirical model to control the quantity of aerosol delivered into the patients lung. An ATOMISOR NL9 M jet nebulizer (La Diffusion Technique Française, France) was filled with terbutaline (Bricanyl, Astra-Zeneca, Sweden) and connected to the inspiratory line of a Horus ventilator (Taema, France). Nebulization was synchronized with the inspiratory phase. We assessed at the end of the endotracheal tube the quantity of terbutaline (terbutaline mass output) and the volume median diameter (VMD) by diffraction-laser method. There was a negative correlation between terbutaline mass output and inspiratory air flow ( r =–0.95, p <0.0001) and between VMD and inspiratory air flow ( r =–0.96, p <0.0001). Moreover, positive end-expiratory pressure levels between 0 cm and 8 cm of water did not significantly change the terbutaline output mass ( p =0.22). Total nebulization time and terbutaline mass output calculated by the mathematical model showed good agreement with experimental data. In conclusion, our semiempirical model allows calculation of the duration of the nebulization required to deliver a given mass of terbutaline into patient lungs.This revised version was published online in May 2005 with a corrected section heading.     

肺部吸入给药制剂及临床应用

目的:分析和综述肺吸入制剂的分类、现状及其临床用药。方法:收集国内外发表出版的相关论文及专著,对肺部吸入给药的特点及临床药物制剂进行了分析总结。结果与结论:肺部吸入给药是防治哮喘、慢性阻塞性肺病等呼吸道疾病的首选给药方式。常见的吸入给药制剂包括定量吸入气雾剂、干粉吸入剂和雾化吸入剂,所用药物主要为β2受体激动剂、抗胆碱药物、吸入性糖皮质激素及复方药物等。     

布地奈德混悬液联合复方异丙托溴铵溶液雾化吸入治疗毛细支气管炎的效果分析

目的探讨吸入用布地奈德混悬液联合吸入用复方异丙托溴铵溶液佐治毛细支气管炎的临床效果。方法将78例毛细支气管炎患儿随机分为两组,对照组采用止咳祛痰、平喘、吸氧、镇静及抗病毒等常规治疗,观察组在对照组基础上,采用吸入用布地奈德混悬液联合吸入用复方异丙托溴铵溶液治疗。比较两组的疗效、喘憋缓解时间、喘鸣音消失时间和肺部湿啰音消失时间。结果观察组的总有效率为82.5%,高于对照组的57.9%,差异有统计学意义（P〈0.05）。两组的喘憋缓解时间、喘鸣音消失时间和肺部湿啰音消失时间比较差异有统计学意义（P〈0.05）。两组用药后均无严重副反应。结论吸入用布地奈德混悬液联合吸入用复方异丙托溴铵溶液治疗毛细支气管炎的效果明显。     

Jet nebulization of prostaglandin E1 during neonatal mechanical ventilation: Stability, emitted dose and aerosol particle size

BACKGROUND: We have previously reported the safety of aerosolized PGE1 in neonatal hypoxemic respiratory failure. The aim of this study is to characterize the physicochemical properties of PGE1 solution, stability, emitted dose and the aerodynamic particle size distribution (APSD) of PGE1 aerosol in a neonatal ventilator circuit. METHODS: PGE1 was diluted in normal saline and physicochemical properties of the solution characterized. Chemical stability and emitted dose were evaluated during jet nebulization in a neonatal conventional (CMV) or high frequency (HFV) ventilator circuit by a high performance liquid chromatography-mass spectrometry method. The APSD of the PGE1 aerosol was evaluated with a 6-stage cascade impactor during CMV. RESULTS: PGE1 solution in normal saline had a low viscosity (0.9818 cP) and surface tension (60.8 mN/m) making it suitable for aerosolization. Little or no degradation of PGE1 was observed in samples from aerosol condensates, the PGE1 solution infused over 24h, or the residual solution in the nebulizer. The emitted dose of PGE1 following jet nebulization was 32-40% during CMV and 0.1% during HFV. The PGE1 aerosol had a mass median aerodynamic diameter of 1.4 microm and geometric S.D. of 2.9 with 90% of particles being <4.0 microm in size. CONCLUSION: Nebulization of PGE1 during neonatal CMV or HFV is efficient and results in rapid nebulization without altering the chemical structure. On the basis of the physicochemical properties of PGE1 solution and the APSD of the PGE1 aerosol, one can predict predominantly alveolar deposition of aerosolized PGE1.     

The effect of continuous intraabdominal nebulization of lidocaine during gynecological laparoscopic procedures- a pilot study

Although laparoscopic surgery is known to cause less postoperative pain when compared to laparotomy, some patients still suffer from excessive pain, especially during the first stages of recovery. The purpose of our study was to assess the effect of intraperitoneal nebulization of lidocaine during gynecological laparoscopic procedures on perioperative pain. The study was a prospective, randomized, double-blinded, placebo-controlled trial (Canadian task force classification I) that included 23 patients who underwent outpatient gynecological laparoscopic procedures. Patients were randomly assigned either to a study group that received 5 mg/kg of lidocaine intraperitonealy during surgery (n=15) or to a control group that received sterile water in the same manner (n=8). The fluid was infuslated along with the CO₂ through a Insuflow® device. All patients received the same anesthetic technique. Intraoperative pain as assessed by changes in the vital signs was treated with fentanyl. Postoperative pain was evaluated according to postoperative opioid requirements and by the Visual Analogue Scale (VAS) at 15 min, 1 h and 24 h postoperatively. The VAS score was found to be lower for the study group 1 h after surgery (p=0.023). There was no difference in the VAS scores at 15 min (p=0.9) and 24 h (p=0.11) after surgery. A correlation analysis showed no association between the amount of lidocaine insufflated and the severity of the postoperative pain. There was no difference in terms of fentanyl administration during surgery or opiod consumption following surgery between the groups. We concluded that continuous intraperitoneal insuflation of lidocaine using an Insuflow® device may significantly reduce pain in the initial stage of postoperative recovery.     

Aerosol therapy in AIDS

Pneumocystis carinii pneumonia (PCP) is the most common presenting symptom in patients with the acquired immunodeficiency syndrome (AIDS). Clinical trials have shown that inhaled pentamidine, delivered by nebulizer, is an effective prophylaxis for PCP in high-risk patients, and can be used to treat mild to moderate episodes. Side effects are minor, in marked contrast to the parenteral route of administration. The choice of nebulizer system will determine both alveolar delivery of pentamidine and the incidence of cough related to deposition of droplets on large conducting airways. Radioaerosol studies have suggested that optimum nebulizer systems for inhaled pentamidine deliver the majority of the aerosol mass in droplets smaller than 2μm diameter, ideal for alveolar penetration.     

Asthma Management Practices at Home in Young Inner-City Children

Information on parental asthma management practices for young children is sparse. The objective of this article is to determine if specific caregiver asthma management practices for children were associated with children's asthma morbidity. Caregivers of 100 inner-city children diagnosed with persistent asthma and participating in an ongoing asthma intervention study were enrolled and interviewed to ascertain measures of asthma morbidity, medication use, health care use (acute and primary care), and asthma management practices. Overall, asthma morbidity was high with almost two thirds of caregivers reporting their child having one or more emergency department visits within the last 6 months and 63% receiving specialty care for their asthma. Appropriate medication use was reported predominantly as albuterol and inhaled steroids (78%). However, only 42% of caregivers reported administering asthma medicines when their child starts to cough and less than half (39%) reported having an asthma action plan. There were no significant differences by asthma severity level for any asthma management practice. In conclusion, caregivers lack knowledge regarding cough as an early asthma symptom. Caregivers should be encouraged to review asthma action plans with health care providers at each medical encounter.     

In vitro deposition properties of nebulized formoterol fumarate: effect of nebulization time,airflow, volume of fill and nebulizer type

ABSTRACT

Objective: The aim of this study was to investigate in vitro the delivery of a new long-acting β₂-agonist (LABA) drug formoterol fumarate inhalation solution (20?µg/2?mL) nebulized with and without ipratropium bromide (0.5?mg/2.5?mL) at different administration times (2.5–22.5?min), airflows (5–28.3?L/min), nebulizer fill volumes (2–6?mL), and nebulizer brands (Pari LC+, Ventstream and DeVilbiss).

Method: Formoterol fumarate with and without ipratropium bromide was aerosolized at different administration times, airflows, nebulizer fill volumes, and nebulizer brands. The drug deposited on the throat, filter and stage plates was collected and analyzed by HPLC to determine the aerodynamic profiles of the nebulized drugs under each variable.

Results: In addition to altering the aerosol characteristics, increasing the nebulizer fill volume including the addition of ipratropium bromide produced a significant (p?<?0.05) increase in the drug output. As expected, sputtering time was significantly longer at low airflows, and vice versa at higher airflows but with a significant loss of drug delivered presumably due to greater solvent evaporation at higher airflows. Airflows between 10 and 28.3?L/min and a nebulization time of approximately 10?min appear sufficient for producing aerosols within the respirable range (1–5?µm MMAD) with the nebulizer/compressor combination used. While the drug output varied significantly (p?<?0.05) among the three brands of nebulizers tested, the LC+ nebulizer appears to produce aerosols (2.7?±?0.1?µm MMAD) capable of penetrating more deeply into the lung than the other nebulizers evaluated under the current test conditions. This study did not attempt to evaluate different nebulizer/compressor combinations. Also, the cascade impaction data may not necessarily reflect aerosol deposition in the airways in vivo, which may be different depending on the health status of the patient.

Conclusion: The results demonstrated that administration of nebulized formoterol fumarate require proper selection of a delivery system/method for safe and effective therapy of the medication with and without ipratropium bromide.