Thesis (Ph.D. in Pharmaceutical Sciences) -- University of Colorado, 2005. / Typescript. Includes bibliographical references (leaves 126-143). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Background: Evidence on aerosol delivery via tracheostomy is lacking. The purpose of this study was to evaluate the effect of aerosol device and administration technique on drug delivery in a simulated spontaneously breathing pediatric model with tracheostomy. Methods: Delivery efficiencies during spontaneous breathing with assisted and unassisted administration techniques were compared using the jet nebulizer (JN- MicroMist), vibrating mesh nebulizer (VMN- Aeroneb Solo) and pressurized metered-dose inhaler (pMDI- ProAirHFA). The direct administration of aerosols in spontaneously breathing patients (unassisted technique) was compared to administration of aerosol therapy via a manual resuscitation bag (assisted technique) attached to the aerosol delivery device and synchronized with inspiration. An in-vitro lung model consisted of an uncuffed tracheostomy tube (4.5 mmID) was attached to a collecting filter (Respirgard) which was connected to a dual-chamber test lung (TTL) and a ventilator (Hamilton). The breathing parameters of a 2 years-old child were set at an RR of 25 breaths/min, a Vt of 150 mL, a Ti of 0.8 sec and PIF of 20 L/min. Albuterol sulfate was administered with each nebulizer (2.5 mg/3 ml) and pMDI with spacer (4 puffs, 108 µg/puff). Each aerosol device was tested five times with both administration techniques (n=5). Drug collected on the filter was eluted with 0.1 N HCl and analyzed via spectrophotometry. Results: The amount of aerosol deposited in the filter was quantified and expressed as inhaled mass and inhaled mass percent. The pMDI with spacer had the highest inhaled mass percent, while the VMN had the highest inhaled mass. The results of this study also found that JN had the least efficient aerosol device used in this study. The trend of higher deposition with unassisted versus assisted administration of aerosol was not significant (p>0.05). Conclusions: Drug deposited distal to the tracheostomy tube with JN was lesser than either VMN or pMDI. Delivery efficiency was similar with unassisted and assisted aerosol administration technique in this in vitro pediatric model.

Introduction: Several problems arise when HMEs are used while giving aerosolized medication including increased airway resistance (Raw) or the need to open the ventilator circuit. Recently, heat and moisture exchangers designed to allow aerosol delivery (HME-AD) have been developed to solve this problem, but no tests have been performed to confirm their effectiveness. The purpose of this study is to evaluate the effect of HME-ADs on aerosol deposition and Raw. Methods: An in-vitro lung model consisting of an 8.0 mm ID endotracheal tube (ETT) connected to a standard ventilator circuit and ventilator was connected to a rubber test lung via cascade humidifier set to deliver 37˚C and 100% relative humidity. The ventilator settings were as follows: Vt 450 ml, RR 20/min, PIF 50 L/min, PEEP 5 cm H2O, and I:E ratio 1:2. HME-ADs used in this study include Circuvent HME/HCH bypass (Smiths-Medical, Keene, NH), Gibeck Humid-Flo HME (Hudson RCI, Arlington Heights, IL), and Airlife BHME (Carefusion, San Diego, CA). As a control, albuterol sulfate (2.5 mg/3mL) was delivered with a vibrating mesh nebulizer (Aeroneb Solo, Aerogen Inc) placed at the wye without any HME-AD in the circuit. Then, the aerosol and HME configurations of each HME-AD were tested by measuring pre-post Raw and aerosol deposition at the end of each run. Each condition was repeated in triplicate (n=3). Aerosol deposition between the aerosol and HME configurations of each HME-AD was compared with a series of student t-tests. Then, differences both in aerosol deposition and in airway resistance among the HME-ADs were analyzed using one-way analysis of variance (ANOVA). Significance was determined as p<0.05. Results: Raw increased after each albuterol treatment with every HME-AD. In the aerosol configuration, the Circuvent and Humid-Flo delivered significantly less aerosol compared to the control (p=.004 and p=.002, respectively), while there was no significant difference on aerosol delivery between the Airlife and the control (p=.084). The Airlife gave the highest aerosol deposition which was not significantly different than control (p=.084). When aerosol delivery between the HME and aerosol configurations in each HME-AD was compared, aerosol deposition with the Humid-Flo was not significantly different (p=.078) but both the Airlife and the Circuvent showed a statistically significant reduction in aerosol deposition with the HME configuration (p=.002 and p=.005). Conclusions: Aerosol delivery and Raw with each HME-AD differ in simulated mechanically ventilated patients. Further studies are needed to determine the effectiveness of these devices over time and with different aerosol generating devices.

Direct reading instruments (DRIs) are popular devices for measuring aerosols because they provide rapid on-site measurement of particle size and/or concentration. However, the output of DRIs may drift over time requiring frequent manufacturer calibration. Given the possibility of drift, the output of DRIs should ideally be verified to ensure proper response before and after field use. Methods for verifying the output of DRIs particle size reading are available for use in laboratory and field. However, methods for verifying the DRIs concentration reading are complex and often use of stationary installations that are not suited for field work. The objective of this study was to develop a verification device that can be used in the field to verify the output of DRIs for measuring aerosol concentration. The new device uses a nebulizer that produces aerosols through vibrating mesh technology. This vibrating mesh nebulizer (VMN) uses only electrical input to generate aerosols and does not require compressed air. The verification device was able to produce stable output of aerosols at low concentrations (0.2 mg/m3 to 1.2 mg/m3). It was also possible to produce different concentration levels of aerosol by changing the electrical current to the VMN. The verification device was used to monitor and validate the output of a condensation particle counter and a photometer. Results showed that both instruments having valid output and did not require manufacture calibration. The verification device made it possible to monitor and verify the output of two DRIs. This was achieved by generating reproducible aerosol output with specific composition. This verification device presents a practical method to verify the concentration output of DRIs for measuring aerosols.

Aerosol administration via small-volume nebulizers are still being used by selected patient-population. In the economic market, several nebulizer designs have become available, with each incorporating unique features that will potentially establish it as the preferred choice in aerosol delivery. With the continuous rising cost of health care services, clinicians are faced with the task of identifying opportunities for cost reduction in respiratory care. PURPOSE: The purpose of this study was to conduct a cost-benefit analysis of dosimetric nebulization using the Circulaire system and the traditional VixOne nebulizer. The desired outcome was to elevate awareness of the potential impact of the Circulaire, and how its adoption might reduce costs and enhance productivity in respiratory care. METHODS: A retrospective study using existing data collected from an urban tertiary adult hospital with a Level II Trauma Center was completed. DATA ANALYSIS: Descriptive statistics were run for each variable. The total cost of a full-time Registered Respiratory Therapist (RRT) with benefits per hour was calculated. The average number of RRTs per 12-hour shift, average number of nebulizer treatments by an RRT per 12-hour shift, average costs of traditional VixOne nebulizer and the Circulaire system were also calculated. RESULTS: Descriptive statistics indicated the annual cost of delivering aerosol therapy using the traditional VixOne nebulizer at 9-minutes treatment time to be $114,263.25 per year. The Circulaire was compared at two different treatment times of 5-minutes and 3-minutes, and the annual costs were $137,422.50 per year and $116,982.50 respectively. A sensitivity analysis was also conducted, and the treatment load was increased by 30%, with a reduction to 5 RRTs per shift. Data indicated an annual savings of 8% with the Circulaire at 5-minutes treatment time, and 21% with the Circulaire at 3-minutes treatment time. CONCLUSION: The use of the Circulaire system at 5-minutes or 3-minutes treatment time can reduce department expenditure by reducing labor costs.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Introdução: A pneumonia associada à ventilação mecânica (PAV) causada por Staphylococcus aureus resistente à meticilina (SARM) é uma infecção nosocomial frequente em pacientes críticos. A vancomicina é o tratamento de escolha, porém tem apresentado altas taxas de falha terapêutica, sendo uma das possíveis causas a baixa penetração no tecido pulmonar após administração intravenosa. Diversos estudos experimentais têm demonstrado que a administração de antibióticos por nebulização possibilita a obtenção de altas concentrações no tecido pulmonar e maior efeito bactericida que a obtida por infusão intravenosa. Entretanto, até o momento, a literatura carece de estudos comparando a utilização de vancomicina por via intravenosa com a via inalatória. Objetivo: O objetivo principal deste estudo foi comparar a concentração de vancomicina atingida no tecido pulmonar saudável após a administração de dose única via intravenosa ou por nebulização, em suínos anestesiados e submetidos à ventilação mecânica. Métodos: Vinte e quatro suínos foram submetidos à anestesia intravenosa, intubação e ventilação mecânica e aleatorimanete distribuidos: Doze animais receberam uma dose única de vancomicina por infusão intravenosa (15 mg.Kg-1), dos quais seis animais foram eutanasiados uma hora após término da administração e seis animais foram eutanasiados após 12 horas e doze animais receberam uma dose única de vancomicina por nebulização com nebulizador de placa vibratória (37,5 mg.Kg-1), dos quais seis animais foram eutanasiados uma hora após término da administração e seis animais foram eutanasiados após 12 horas. Foram coletadas amostras de sangue para dosagem sérica de vancomicina antes da administração em 30\', 1, 2, 4, 6, 8 e 12h após o término da administração. Após a eutanásia, foram coletadas amostras de tecido pulmonar de regiões dependentes e não dependentes para dosagem tecidual de vancomicina. Nos animais que receberam a vancomicina por nebulização, a deposição extrapulmonar deste antibiótico foi calculada após da lavagem das partes do circuito ventilatório e da câmara de nebulização. A dosagem de vancomicina foi realizada por meio de cromatografia líquida de alta eficiência (CLAE-UV). Resultados: A concentração de vancomicina no tecido pulmonar obtida no grupo nebulizado de uma hora foi aproximadamente treze vezes maior que a concentração pulmonar obtida no grupo intravenoso de uma hora; (mediana e intervalo interquartílico) 161 (71-301) vs. 12 (4-42) Mig.g-1 (p < 0,05), respectivamente. A concentração pulmonar de vancomicina no grupo nebulizado de 12 horas foi 63 (23-119) Mig.g-1 e níveis indetectáveis de vancomicina foram obtidos no grupo intravenoso de 12 horas; 0 (0-19) Mig.g-1 (p < 0,05). Houve ausência de um pico sérico de vancomicina após o término da administração por nebulização no grupo de doze horas comparado ao grupo intravenoso. Conclusão: A administração de vancomicina por nebulização apresentou maiores concentrações pulmonares do que pela via intravenosa. Os resultados sugerem uma passagem lentificada da vancomicina pela barreira alvéolo-capilar após nebulização / Introduction: Ventilator-associated pneumonia caused by Staphylococcus aureus methicillin resistant is a frequent nosocomial infection in critically ill patients. Vancomycin is the treatment of choice, but it has presented high rates of therapeutic failure, possibly due to its low penetration in lung tissue following intravenous administration. Many studies have shown that lung tissue deposition and antibacterial efficiency of nebulized antibiotics were greater than by intravenous administration. However, to date, the literature lacks studies comparing the use of vancomycin intravenously with the inhalation route Objective: The aim of this study was to compare vancomycin concentration in healthy lungs after a single dose nebulized or intravenously administered in anesthetized and ventilated piglets. Methods: Twenty four piglets were anesthetized, intubated and submitted to mechanical ventilation. Twelve animals received a single dose of vancomycin by intravenous infusion (15 mg.kg-1), of which six animals were euthanized one hour after the end of administration and six animals were euthanized after 12 hours and twelve animals received a single dose of vancomycin using a vibrating plate nebulizer (37,5 mg.kg-1), of which six animals were euthanized one hour after the end of administration and six animals were euthanized after 12 hours. Blood samples were collected for serum vancomycin dosage before and at 30\', 1, 2, 4, 6, 8 and 12 hours after the end of administration. After euthanasia, tissue samples from dependent and non-dependent lung tissue were collected for tissue dosage of vancomycin. In animals receiving vancomycin by nebulization, the extrapulmonary deposition of this antibiotic was calculated after washing the parts of the ventilator circuit and the nebulization chamber. The dosage of vancomycin was performed using high performance liquid chromatography (HPLC-UV). Results: Vancomycin lung tissue concentrations in one-hour aerosol group were thirteen times greater than pulmonary concentration in one-hour intravenous group (median and interquartile range): 161 (71-301) Mig.g-1 vs. 12 (4-42) Mig.g-1 (p < 0.05). Vancomycin lung tissue concentration in twelve-hour aerosol group was 63 (23-119) ?g.g-1 and it was undetectable in twelve-hour intravenous group; 0 (0-19) Mig.g-1 (p < 0.05). There was no vancomycin serum peak following the end of administration by nebulization in the 12-hour group compared to intravenous administration. Conclusion: Administration of vancomycin by nebulization showed higher lung tissue concentrations than intravenous route. The results suggest a slower passage of vancomycin through alveolar capillary barrier after nebulization

Introdução: A pneumonia associada à ventilação mecânica (PAV) causada por Staphylococcus aureus resistente à meticilina (SARM) é uma infecção nosocomial frequente em pacientes críticos. A vancomicina é o tratamento de escolha, porém tem apresentado altas taxas de falha terapêutica, sendo uma das possíveis causas a baixa penetração no tecido pulmonar após administração intravenosa. Diversos estudos experimentais têm demonstrado que a administração de antibióticos por nebulização possibilita a obtenção de altas concentrações no tecido pulmonar e maior efeito bactericida que a obtida por infusão intravenosa. Entretanto, até o momento, a literatura carece de estudos comparando a utilização de vancomicina por via intravenosa com a via inalatória. Objetivo: O objetivo principal deste estudo foi comparar a concentração de vancomicina atingida no tecido pulmonar saudável após a administração de dose única via intravenosa ou por nebulização, em suínos anestesiados e submetidos à ventilação mecânica. Métodos: Vinte e quatro suínos foram submetidos à anestesia intravenosa, intubação e ventilação mecânica e aleatorimanete distribuidos: Doze animais receberam uma dose única de vancomicina por infusão intravenosa (15 mg.Kg-1), dos quais seis animais foram eutanasiados uma hora após término da administração e seis animais foram eutanasiados após 12 horas e doze animais receberam uma dose única de vancomicina por nebulização com nebulizador de placa vibratória (37,5 mg.Kg-1), dos quais seis animais foram eutanasiados uma hora após término da administração e seis animais foram eutanasiados após 12 horas. Foram coletadas amostras de sangue para dosagem sérica de vancomicina antes da administração em 30\', 1, 2, 4, 6, 8 e 12h após o término da administração. Após a eutanásia, foram coletadas amostras de tecido pulmonar de regiões dependentes e não dependentes para dosagem tecidual de vancomicina. Nos animais que receberam a vancomicina por nebulização, a deposição extrapulmonar deste antibiótico foi calculada após da lavagem das partes do circuito ventilatório e da câmara de nebulização. A dosagem de vancomicina foi realizada por meio de cromatografia líquida de alta eficiência (CLAE-UV). Resultados: A concentração de vancomicina no tecido pulmonar obtida no grupo nebulizado de uma hora foi aproximadamente treze vezes maior que a concentração pulmonar obtida no grupo intravenoso de uma hora; (mediana e intervalo interquartílico) 161 (71-301) vs. 12 (4-42) Mig.g-1 (p < 0,05), respectivamente. A concentração pulmonar de vancomicina no grupo nebulizado de 12 horas foi 63 (23-119) Mig.g-1 e níveis indetectáveis de vancomicina foram obtidos no grupo intravenoso de 12 horas; 0 (0-19) Mig.g-1 (p < 0,05). Houve ausência de um pico sérico de vancomicina após o término da administração por nebulização no grupo de doze horas comparado ao grupo intravenoso. Conclusão: A administração de vancomicina por nebulização apresentou maiores concentrações pulmonares do que pela via intravenosa. Os resultados sugerem uma passagem lentificada da vancomicina pela barreira alvéolo-capilar após nebulização / Introduction: Ventilator-associated pneumonia caused by Staphylococcus aureus methicillin resistant is a frequent nosocomial infection in critically ill patients. Vancomycin is the treatment of choice, but it has presented high rates of therapeutic failure, possibly due to its low penetration in lung tissue following intravenous administration. Many studies have shown that lung tissue deposition and antibacterial efficiency of nebulized antibiotics were greater than by intravenous administration. However, to date, the literature lacks studies comparing the use of vancomycin intravenously with the inhalation route Objective: The aim of this study was to compare vancomycin concentration in healthy lungs after a single dose nebulized or intravenously administered in anesthetized and ventilated piglets. Methods: Twenty four piglets were anesthetized, intubated and submitted to mechanical ventilation. Twelve animals received a single dose of vancomycin by intravenous infusion (15 mg.kg-1), of which six animals were euthanized one hour after the end of administration and six animals were euthanized after 12 hours and twelve animals received a single dose of vancomycin using a vibrating plate nebulizer (37,5 mg.kg-1), of which six animals were euthanized one hour after the end of administration and six animals were euthanized after 12 hours. Blood samples were collected for serum vancomycin dosage before and at 30\', 1, 2, 4, 6, 8 and 12 hours after the end of administration. After euthanasia, tissue samples from dependent and non-dependent lung tissue were collected for tissue dosage of vancomycin. In animals receiving vancomycin by nebulization, the extrapulmonary deposition of this antibiotic was calculated after washing the parts of the ventilator circuit and the nebulization chamber. The dosage of vancomycin was performed using high performance liquid chromatography (HPLC-UV). Results: Vancomycin lung tissue concentrations in one-hour aerosol group were thirteen times greater than pulmonary concentration in one-hour intravenous group (median and interquartile range): 161 (71-301) Mig.g-1 vs. 12 (4-42) Mig.g-1 (p < 0.05). Vancomycin lung tissue concentration in twelve-hour aerosol group was 63 (23-119) ?g.g-1 and it was undetectable in twelve-hour intravenous group; 0 (0-19) Mig.g-1 (p < 0.05). There was no vancomycin serum peak following the end of administration by nebulization in the 12-hour group compared to intravenous administration. Conclusion: Administration of vancomycin by nebulization showed higher lung tissue concentrations than intravenous route. The results suggest a slower passage of vancomycin through alveolar capillary barrier after nebulization

Pacientes com fibrose cística (FC) apresentam infecções respiratórias recorrentes e crônicas por patógenos peculiares e realizam inalações diariamente como parte de seu tratamento. É reconhecido que patógenos específicos são comumente isolados nestes nebulizadores e existe uma preocupação de que estes equipamentos possam contribuir como fonte de infecção bacteriana para as vias aéreas inferiores. Objetivo: Descrever os patógenos encontrados nos nebulizadores de uso domiciliar e nas amostras de trato respiratório de pacientes com FC e verificar a eficácia de uma técnica padronizada de higiene e desinfecção destes nebulizadores na redução da contaminação dos mesmos. Método: Quarenta pacientes com FC (22M:18F) com mediana de idade de 11,2 ± 3,74 anos e que utilizavam o nebulizador PRONEB/sistema PARI foram incluídos no estudo. Amostras dos nebulizadores foram coletadas do bocal e do copo reservatório utilizando-se um swab estéril umedecido em solução salina estéril. As amostras de trato respiratório dos pacientes foram colhidas por expectoração em coletor estéril ou com swab de orofaringe após estímulo de tosse. As culturas foram realizadas em meios seletivos e a identificação bacteriana feita através de provas bioquímicas clássicas. Instruções verbais e escritas de higiene e desinfecção dos nebulizadores foram ministradas. Resultados: A contaminação de alguma parte dos nebulizadores foi observada em 23/40 casos (57,5%). A contaminação do bocal e do copo foi similar, observada em 16 e 19 casos, respectivamente. Os patógenos mais comumente identificados foram Bacilos Gram negativos não fermentadores (sem identificação) (14), Staphylococcus coagulase negativo (13), Leveduras (12), Enterobacter sp. (5), Pseudomonas putida (7) e complexo Burkholderia cepacia (3). Nas amostras de trato respiratório houve um predomínio de Staphylococcus aureus (29), seguido de Pseudomonas aeruginosa (20) e complexo Burkholderia cepacia (3). Em 4 casos observou-se a identificação de um mesmo patógeno em amostras do nebulizador e do trato respiratório. Uma redução significativa da contaminação (43,5%) foi encontrada após instrução de técnica padronizada de higiene e desinfecção dos nebulizadores, num prazo médio de reavaliação de dois meses. Conclusões: A prevalência de contaminação dos nebulizadores é alta, o que indica a necessidade de melhoria nas práticas de higiene e desinfecção dos nebulizadores de pacientes com FC. Uma única intervenção educacional pode ter impacto significativo / Patients with cystic fibrosis (CF) have chronic and recurrent respiratory infections by peculiar pathogens and perform inhalations daily as part of their treatment. It is recognized that specific pathogens are commonly isolated in these nebulizers and there is concern that these devices can contribute as a source of bacterial infection to the lower airways. Objective: To describe the pathogens found in home use of nebulizers and in respiratory samples of CF patients and evaluate the effectiveness of a standardized hygiene and disinfection in reducing the contamination. Methods: Forty patients with CF (22M: 18F) with a median age of 11.2 ± 3.74 years and who used the nebulizer Proneb / PARI system were included in the study. Samples were collected from the nebulizer mouthpiece and cup container using a sterile swab moistened with sterile saline. The respiratory samples of patients were collected by expectoration into a sterile swab or oropharyngeal after stimulation of cough. The cultures were performed on selective media and bacterial identification made by classical biochemical tests. Written and oral instructions regarding cleaning and disinfection of nebulizers were provided. Results: The contamination of any part of the nebulizer was observed in 23/40 cases (57.5%). Contamination of the mouthpiece and the cup container was similarly observed on 16 and 19 cases, respectively. The pathogens most commonly identified were Gram negative fermenters (unmarked) (14), coagulase-negative Staphylococcus (13), yeast (12), Enterobacter sp. (5) Pseudomonas putida (7) and Burkholderia cepacia (3). In respiratory samples there was a predominance of Staphylococcus aureus (29), followed by Pseudomonas aeruginosa (20) and Burkholderia cepacia (3). In four cases we observed the same identifying a pathogen in samples of the nebulizer and the respiratory tract. A significant reduction of contamination (43,5%) was found after instruction of standard procedures of hygiene and disinfection of nebulizers, within an average of two months revaluation. Conclusions: The prevalence of contamination of nebulizers is high, which indicates the need for improvement in hygiene practices and disinfection of nebulizers for patients with CF. A single educational intervention may have significant impact