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Efficacy of nebulized budesonide compared to oral prednisolone in acute bronchial asthma.

To evaluate the efficacy of nebulized budesonide compared to oral prednisolone early in the emergency room management of acute asthma, we conducted a double-blind, placebo-controlled trial. Eighty children, 2 years to 12 years of age, with acute moderate attacks of asthma, were randomized into two groups. One group received nebulized salbutamol (0.15 mg/kg) and placebo at half-hourly intervals for three doses, and a single dose of oral prednisolone (2 mg/kg) (prednisolone group) and other group received three doses of nebulized salbutamol and budesonide (800 microg) at half-hourly intervals and a single dose of placebo tablets (budesonide group). The baseline characteristics of the two groups were similar, but after three doses of nebulization oxygen saturation, respiratory rate, pulmonary index and respiratory distress score were significantly improved in the budesonide group compared to prednisolone group (p < 0.01). The proportion of patients who were fit for discharge at the end of 2 h after the third dose of nebulization was significantly higher in the budesonide group than in the prednisolone group (22/ 41, 54% vs 7/39, 18%, p < 0.001). The data suggest that a combination of nebulized salbutamol and budesonide should be preferred in the emergency room management of children with acute moderate to severe exacerbation of asthma and who are not on prior oral or inhaled steroid therapy.

Administration, Inhalation↗

Nebulized fluticasone propionate vs. budesonide as adjunctive treatment in children with asthma exacerbation.

OBJECTIVES: To compare the effects of nebulized fluticasone propionate (FP) and nebulized budesonide (BUD) in addition to inhaled salbutamol in children with mild asthma exacerbation. METHODS: The study was a multicenter, randomized, single-blind, parallel group design. One hundred and sixty-eight children, aged 4-15 years, were randomly allocated to receive either nebulized FP (250 mcg) or nebulized BUD (500 mcg) twice daily for 10 days. On presentation, at the end of treatment, and after a 7-day follow-up, clinical assessment and pulmonary function measurements were performed. Daytime and nighttime asthma symptom scores, the use of rescue salbutamol, and morning/evening peak expiratory flow (PEF) values were recorded at home during the treatment period. Morning cortisol concentration (51 children) and overnight urinary cortisol excretion (30 children) were also measured in six centers at the start and at the end of the treatment. RESULTS: Improvement of morning PEF was significantly higher in patients treated with FP (p=0.032). The percentage of symptom-free nights was significantly higher in the BUD group (p=0.006), but no difference was found in symptom-free days. No intergroup difference was detected in the percentage of days/nights free from rescue medication and in pulmonary function tests performed in outpatient settings. There was no evidence of hypothalamo-pituitary-adrenal axis suppression. CONCLUSIONS: A short course of nebulized FP has the same effects as a double dose of nebulized BUD, when either drug is added to bronchodilator therapy in children with mild asthma exacerbation

Adolescent↗

Aerosol characterization of nebulized intranasal glucocorticoid formulations.

Inhaled glucocorticoids (GCs) are the mainstay of long-term therapy for asthma. The lack of suitable preparations in the United States has induced clinicians to use intranasal (IN) GC formulations as "nebulizer suspensions" for off-label therapy. However, no data are available regarding aerosol production and characteristics. The aim of this study was to characterize drug outputs and aerodynamic profiles of four nebulized IN GC formulations with further analysis of flunisolide (Flu), and to test the influence of different delivery system/formulation combinations. The aerodynamic profiles and drug outputs were determined by impaction and chemical analysis. The solution output was determined by the gravimetric technique. Triamcinole acetonide (TAA), fluticasone propionate (Flut), beclomethasone dipropionate (Bec), and Flu (550, 500, 840, and 250 microg, respectively) diluted to 4 mL with saline solution were tested with the Sidestream (SID) and Aero-Tech II (AT2) nebulizers. Subsequently, Flu was tested with four additional nebulizers (Pari LC + [PARI] Acorn II, Hudson T Up-draft II, and Raindrop). All the aerosols were heterodisperse and had a particle size range optimal for peripheral airway deposition (1.85 to 3.67 microm). Flu had the highest drug output in the respirable range (22.8 and 20.3 microg/min with the AT and SID, respectively). Flu was 5-11 times more efficiently nebulized than the other formulations tested. No differences were detected in the solution outputs (0.25 to 0.3 mL/min). In subsequent testing of Flu, the PARI, AT, and SID showed the best performances. The LC+ achieved the highest drug and solution output (27.4 microg/min and 0.89 mL/min, respectively). In conclusion, Flu showed the best aerosol performance characteristics. These data do not endorse the off-label utilization of nebulized IN GC, but underscores the importance of in vitro testing before selecting any formulation/nebulizer combinations for clinical use.

Administration, Inhalation↗

Effect of driving pressure and nebulizer model on aerosol output during intermittent delivery with a dosimeter.

Recent guidelines reinforce the need for a standardized technique during inhalational bronchoprovocation challenge testing. We investigated the effects of nebulizer model and dosimeter driving pressure on nebulizer output using a nebulized saline model. Four nebulizers (Hudson 1720, Salter 8900, Baxter Airlife, and DeVilbiss 644) were evaluated at two driving pressures (20 and 50 pounds per square inch [psi]) via a dosimeter (Salter 700) that delivered a 0.6-sec actuation. Output was determined gravimetrically after 20 actuations of saline at constant respiratory flow and volume. Output per actuation at 20 psi was 2.83 +/- 0.41 mg (mean +/- SD), 4.58 +/- 0.66, 4.75 +/- 0.42, and 4.75 +/- 1.37 for the Hudson, Salter, Baxter, and DeVilbiss, respectively, and 6.75 +/- 0.61 mg, 9.17 +/- 0.88, 9.42 +/- 1.32, and 9.83 +/- 1.75 at 50 psi. The Hudson delivered a lower volume than the other nebulizers (p < 0.0005). At 20 psi, output from the DeVilbiss had greater variability (coefficient of variation = 28.8%) compared to the Baxter (CV = 8.8%; p = 0.045). The output was greater at 50 psi than 20 psi for all models (p < 0.0005). These results demonstrate that, when choosing a nebulizer driven by a dosimeter, it is important to base that selection on published data describing aerosol output under different driving pressures.

Aerosols↗

An investigation of in vitro/in vivo correlations for salbutamol nebulized by eight systems.

The choice of a nebulized system for a patient usually depends on the equipment available. To date, there is limited guidance on the selection and use of a nebulizer. We have conducted in vitro tests described within the draft European Standard for Nebulisers (BSEN13544-1; CEN) and correlated these to in vivo pharmacokinetic performance of relative lung and systemic deposition in healthy volunteers. Eight nebulizer systems have been tested. The in vitro analysis used the recommended CEN methods to quantify the total dose available for inhalation as well as the size distribution from which the respirable dose was determined. The draft European Standard methods were slightly modified to use salbutamol rather than a fluoride tracer. For the in vivo study, nine volunteers provided urine samples after 30 min and then pooled for 24 h after the start of each nebulized dose (2.5 mg of salbutamol). Amounts of salbutamol and its metabolite excreted in the urine samples were determined. There was a significant (p = 0.02) correlation between the in vitro respirable dose and the amount of salbutamol excreted in the urine 30 min after the start of nebulization (relative bioavailability of salbutamol to the lung). Also, there was a significant (p < 0.001) correlation between the in vitro dose available for inhalation and the total amount of salbutamol and its metabolites excreted over the 24 h after the start of nebulization (relative bioavailability of salbutamol to the body). The results demonstrate that in vivo/in vitro correlations exist and warrant further investigations. The in vitro methods require further validation with in vivo correlations using patients with different severities of airway obstruction.

Aerosols↗

The effect of breathing pattern on nebulizer drug delivery.

The significance of using breathing patterns with simplified functional shapes in vented jet nebulizer research is examined. This study is comprised of three parts: (1) The measurement and analysis of human breathing patterns, (2) the subsequent in vitro testing of the effects of breathing pattern differences using a consistent bench test method, and (3) a computer modeling of these effects on the estimated regional drug deposition in the human lung. Breathing through a Pari LC-Star nebulizer caused statistically significant changes (p < or = 0.05) in measured human breathing patterns when compared to normal breathing. Observed changes included an increase in the tidal volume (34%) and period (39%). Additionally, the average duty cycle shifted 12% towards a more symmetrical breath due to the unequal increase in the inhalation and exhalation times (55% and 28%, respectively). The position of the point of maximum flow in each breath phase shifted towards the beginning and end of the breath for the inhale and exhale by 28% and 48%, respectively. The bench testing revealed that breathing pattern shape variation caused statistically significant differences in nebulizer output only in two cases. Decreasing duty cycles and shifting the point of maximum flow towards the beginning of the breath both result in a decrease in output efficiency. Square flow patterns produced slight but consistently higher output efficiencies (average 2.1% higher) and a constant output particle size over the course of each breath, different from the other non-square patterns. Numerical simulations revealed no significant dosage differences resulting from breathing pattern shape variations. However, square wave patterns consistently produced slight overpredictions in comparison with real nebulizer patterns. In contrast, sine wave patterns were found to produce essentially the same results as nebulizer patterns in both the bench tests and in the deposition simulations. This suggests that sine wave shapes are preferable for simulating breathing when bench testing drug delivery using vented jet nebulizers.

Adult↗

Effect of excipients on the stability and aerosol performance of nebulized aviscumine.

Pulmonary delivery is an attractive alternative route to deliver protein drugs that are currently delivered by injection. Inhalation therapy via nebulizers is a well accepted way for pulmonary application of proteins considering the formulation difficulties of MDIs or DPIs. This research presents the effect of variable excipients on the stability and aerosol performance of freeze-dried aviscumine after reconstitution and nebulization. Aviscumine formulations containing 100 mmol/L Tris buffer, 0.1% (w/v) Polysorbate 80, 0.01% (w/v) Na(2)-EDTA and 8% (w/v) Hydroxyethyl starch have been lyophilized and reconstituted with a buffered isotonic solution pH 8. The aviscumine activity was determined by a binding assay directly after reconstitution and after nebulization with a PariBoy air-jet nebulizer, a Multisonic and a Systam ultrasonic nebulizer. The stabilization of aviscumine by the addition of variable buffer salts to the reconstitution medium, such as 50, 100, and 200 mmol/L Tris buffer, 20 and 100 mmol/L phosphate buffer, and 20 and 100 mmol/L Tricine buffer, was studied. About 50% of aviscumine activity was lost after 20 min nebulization time without any additives. Nevertheless, higher buffer concentrations confer greater stability. About 70% of the aviscumine activity could be retained by the addition 0.03% octanoyl-N-methylglucamide and 100 mmol/L Tricine to the reconstitution medium.

Administration, Inhalation↗

Delivery and retention of an insulin aerosol produced by a new jet nebulizer.

UNLABELLED: This study describes the delivery and distribution of an aerosol generated by a jet nebulizer (MAXIN) in an experimental animal model. Anesthetised, intubated and ventilated piglets inhaled radiolabeled technetium diethylene-triamine-penta-acetic acid (99mTc-DTPA) through the endotracheal tube. The lungs were excised en bloc and scintigraphed, using a computerized gamma camera to evaluate the pattern of distribution. By nebulizing radiolabeled 125I-insulin and comparing the activity deposited on inspiratory and expiratory electrostatic filters, delivery and retention of nebulized insulin was assessed. The distribution of aerosol in the lungs was very even and reached the most peripheral parts. The delivery of nebulized insulin was calculated to be 88.9 +/- 5.3% and 36.1 +/- 8.8% of the insulin delivered to the respiratory tract was retained. The immediate local effects of insulin aerosol administration on the lungs were evaluated using light microscopy. No adverse effects were observed at histopathologic examination of the lung tissue. CONCLUSION: This study shows a high penetration of aerosol to the peripheral parts of the lung and efficient delivery of nebulized insulin when using the MAXIN-nebulizer.

Aerosols↗

Acute pulmonary effects of three nebulizers for administering aerosol pentamidine: comparison of Parineb to Fisoneb and Respirgard II.

We conducted a prospective, unblinded, nonrandomized, multiple crossover study to assess the acute pulmonary effects of a new jet nebulizer-Parineb, comparing it to Respirgard II (jet nebulizer) and Fisoneb (ultrasonic nebulizer) for administering aerosol pentamidine (AP). Twenty-three HIV patients received AP at 60 mg dissolved in 3 ml sterile water with Parineb and Fisoneb and 300 mg dissolved in 5 ml sterile water with Respirgard II on three successive clinic visits. Twelve patients known to develop bronchospasm with AP received 200 micrograms of salbutamol as premedication for all three nebulizers. Eleven subjects received AP without bronchodilator premedication. All subjects had a reduction in flow rates with AP. No significant difference was noted in the reduction of flow rates between the three nebulizers in those patients without prior history of bronchospasm with AP. However, there was a significantly greater reduction in flow rates with Parineb in patients with known AP-induced bronchospasm despite premedication with bronchodilator. This decrease in flow rates with Parineb was not felt by patients based on the subjective rating of cough using a visual analog score when compared to the other two nebulizers. Parineb should be used cautiously in individuals with known AP-induced bronchospasm.

Administration, Inhalation↗

Accounting for radioactivity before and after nebulization of tobramycin to insure accuracy of quantification of lung deposition.

The ability to predict drug deposition of inhaled drugs used in cystic fibrosis (CF) is important if there is a need to target specific doses of drug to the lungs of individual patients. The gold standard of measuring pulmonary deposition is the quantification of an aerosolized radiolabel either mixed with the drug solution or tagged directly to the compound of interest. Accuracy of the quantification could be assured if there is agreement between the amount of radioactivity before and after administration. Before administration, the radiolabel is concentrated in the well of the nebulizer, whereas after administration, it is distributed throughout the nebulizer, the expiratory filter and connectors, and the upper airway, stomach, trachea, and lung. Not only is the geometry of the distribution that is presented to the gamma camera different, but there are different attenuation factors for the various body tissues. The primary aim of this study was to evaluate the accuracy of the quantification of deposition. Secondary goals were to compare in vitro nebulizer performance with that measured in vivo during the deposition study. Eighty milligrams of tobramycin and technetium bound to human serum albumin was administered to 10 normal adults using a Pari LC Jet Plus (Pari Respiratory Equipment, Inc., Richmond, VA) breath-enhanced nebulizer. Techniques were developed that allowed for the accounting of 99 +/- 2% of the initial radioactivity. The fraction of the rate of lung deposition to total body deposition was the in vivo respirable fraction (0.62 +/- 0.07), which closely agreed with in vitro measurements of respirable fraction (0.62 +/- 0.04). Drug output measured from the change in weight and concentration in the nebulizer systematically overestimated drug output measured by the deposition study. The results indicate that 11.8 of the initial 80 mg would be deposited in the lungs. This technique could be adapted to accurately quantify the amount of deposition on any inhaled therapeutic agent, but caution must be used when extrapolating performance of a nebulizer on the bench to expected deposition in patients.

Adult↗

Community survey of home nebulizer technique by elderly people.

To determine the prevalence and nature of difficulties elderly subjects experience using home nebulizers we have studied all patients in the Leeds Health District aged 70 years and older loaned a nebulizer from the hospital for at least 6 months. Of 42 subjects with a nebulizer, 40 (95%) agreed to assessment. They had a mean age of 79 years (range 70-84 years) and mean duration of nebulizer use of 38 months (range 6-120 months). Twenty subjects had one or more problems with 14/40 (35%) rated as moderate or severe; difficulties with cleaning 16/40 (40%) and filling 7/40 (18%) were the most frequent; 13/40 (33%) were sometimes or always dependent on their carers to administer their nebulizers. Elderly subjects often experience practical difficulties, or require help from a carer, when using a home nebulizer.

Activities of Daily Living↗

Upper airway reactivity and upper respiratory tract infection: effect of nebulized lidocaine.

Patients presenting for elective anaesthesia and surgery may be suffering with, or recovering from, a recent upper respiratory tract infection. Airway reflexes are heightened and these individuals may be more likely to suffer airway complications on administration of general anaesthesia. We have examined the effect of nebulized lidocaine on upper airway reflexes in such subjects. Using dilute ammonia as a chemical stimulus to the upper airway, we measured upper airway reactivity in 15 volunteers (aged 22-43 yr) with symptoms of an upper respiratory tract infection for 4 days or less. The threshold concentration of ammonia producing a brief reduction in inspiratory flow was determined. Measurements were made before and after administration of a nebulized solution of 4% lidocaine 4 ml or saline. After a 2-h interval the procedure was repeated with the alternative solution. The order of administration was randomized. The observer was blind to the solution given. Ammonia threshold was found to increase in subjects after nebulized lidocaine, from a median value of 327 (range 76-878) ppm to 878 (251-1620) ppm (P = 0.0007, Wilcoxon); there was no significant change after nebulized saline. After a convalescence period of at least 4 weeks, with no return of symptoms in the preceding 2 weeks, ammonia threshold was reassessed. It was found to be increased in all 15 subjects. Comparison of the five different times of measurement showed a highly significant difference (P < 0.001, Friedman). Subsequent analysis showed significant differences (P < 0.05, Wilcoxon) between convalescent ammonia threshold and both baseline and post-saline nebulizer values. There was no significant difference between convalescent and post-lidocaine ammonia threshold. We conclude that in adult subjects, nebulized lidocaine attenuated the heightened airway reflex sensitivity associated with symptoms and signs of upper respiratory tract infection.

Adult↗

Choosing a nebulizer for cystic fibrosis applications.

As the number of inhaled drugs available for cystic fibrosis grows, there is increasing awareness of delivery device issues. Current jet and ultrasonic nebulizers are inefficient at delivering drugs to the lower respiratory tract. There are large differences in output characteristics between nebulizers and high intersubject variability in lung deposition. The clinical effects of inhaled drugs depend on adequate dosing to the lower airway, so we must choose a nebulizer and patient characteristics that will affect lung deposition positively. Aerosols with particle sizes at the smaller end of the respirable range (2 to 3 microns) may enhance the clinical benefit of some drugs, regardless of patient age or disease severity. Breath-enhanced (Venturi) jet nebulizers are less wasteful than constant-output nebulizers and perform better than conventional nebulizers with many drugs. Patient breathing patterns and degree of airway obstruction are important in determining the site of airway deposition. With increased attention to aerosol delivery issues by clinicians, industry, and regulatory agencies, improved technologies will evolve to target therapies to the lung.

Aerosols↗

Continuous nebulized albuterol attenuates acute lung injury in an ovine model of combined burn and smoke inhalation.

OBJECTIVE: Albuterol, due to its bronchodilatory and anti-inflammatory effects, is given via continuous nebulization in children with severe asthma. Combined burn and smoke inhalation injury frequently results in acute lung injury due to a combination of airway obstruction and inflammation. We hypothesized that albuterol administered via continuous nebulization would mitigate acute lung injury after smoke inhalation injury and burn. DESIGN: Randomized prospective animal model. SUBJECTS: Twenty adult female sheep (mean weight, 33.1+/-0.9 kg). INTERVENTIONS: Adult ewes were subjected to a 40% body surface area third-degree flame burn and smoke inhalation injury after tracheostomy. Sheep were allocated to a) sham group, b) saline continuous nebulization group, c) 20 mg of albuterol continuous nebulization group, or d) 40 mg of albuterol continuous nebulization group (n=5 animals per group). All groups received intravenous lactated Ringer's solution at 4 mL.kg-1.%burn(-1).24 hrs-1 for resuscitation and were equally mechanically ventilated throughout the 48-hr study period. Pulmonary and cardiac function, lung lymph flow, bronchial obstruction score, and wet/dry lung weights were recorded. RESULTS: Compared with saline and control groups, the albuterol groups had lower pause and peak inspiratory pressures, decreased pulmonary transvascular fluid flux, a significantly higher Pao2/Fio2 ratio, and decreased shunt fraction at 48 hrs postinjury. The wet-to-dry lung weight ratio and bronchial obstruction scores were lower for sheep receiving albuterol. CONCLUSIONS: Continuous nebulization of albuterol improves pulmonary function via improved airway clearance and decreased fluid flux in a combined burn/smoke inhalation injury model.

Administration, Inhalation↗

Misleading high tobramycin plasma concentrations can be caused by skin contamination of fingerprick blood following inhalation of nebulized tobramycin (TOBI): a short report.

We observed unexpected high plasma concentrations of tobramycin (48.5 and 28.1 mg/L) in fingerprick blood samples after the nebulization of tobramycin solution for inhalation (tobramycin 300 mg/5 mL, TOBI by 2 young children aged 3 years. To investigate whether dermal contamination could be the source of error, 3 adult volunteers were present during another nebulization by a third child (age 2 years). The volunteers had exposure to tobramycin by handling the nebulizer or the nebule and also by inhalation from holding the child and being in close proximity while TOBI was being administered. Five blood samples by fingerprick and 2 by venipuncture were collected and assayed for tobramycin concentration. On each occasion the site was swabbed with alcohol wipes to mimic standard patient sampling methods. One site was resampled after cleaning of hands with 2% chlorhexidine gluconate and water. Tobramycin concentrations from venipuncture 1-2 hours after nebulization were all <0.2 mg/L except for 1 result of 1.2 mg/L. The tobramycin concentrations from fingerpricks before hand washing varied between 6.8 and 172 mg/L, and after hand washing between 0.3 and 17.6 mg/L. Contamination of fingers with tobramycin is likely to have caused the error in the 2 initial cases and did cause misleadingly elevated levels in the adult volunteers. We caution that therapeutic drug monitoring of nebulized tobramycin should not be done by fingerprick sampling, and care should be taken to avoid contamination of the venipuncture site.

Child, Preschool↗

Effects of manganese superoxide dismutase nebulization on pulmonary function in an ovine model of acute lung injury.

Smoke inhalation injury is a major cause of morbidity and mortality in thermally injured individuals. There is evidence of increased oxygen free radical activity, e.g., superoxide, in association with smoke inhalation injury. Because superoxide dismutase converts the reactive superoxide radical to peroxide, we hypothesized that nebulization of manganese superoxide dismutase (Mn-SOD) into the airway might attenuate pulmonary dysfunction secondary to smoke inhalation injury. The present study was designed as a prospective, controlled, and randomized laboratory experiment to determine the effects of aerosolized Mn-SOD on lung fluid balance, as indexed by changes in pulmonary microvascular permeability, lung lymph flow (Q(L)), and gas exchange in an established and clinically relevant ovine model of smoke inhalation injury. Fifteen female Merino sheep were chronically instrumented with a femoral arterial, a Swan-Ganz, and a left atrial catheter. In addition, the right caudal mediastinal lymph node was cannulated to measure Q(L) (mL.h(-1)). Pneumatic occluders were placed around the right pulmonary veins for the determination of the reflection coefficient (sigma). After 7 days of recovery, sheep were randomly allocated to (a) an untreated control group (4 groups of 12 breaths of cotton smoke), (b) an injured group treated with nebulized Mn-SOD (5 mg/kg), and (c) an injured group that received only the vehicle (nebulized saline). Nebulization was performed 1 h and 12 h after smoke inhalation. Mn-SOD nebulization attenuated the increase in both filtration coefficient and sigma and significantly decreased lung tissue conjugated dienes. However, there were no differences in Q(L), PaO2/FiO2 ratio, and bloodless lung wet/dry weight ratio between groups. Although Mn-SOD nebulization attenuated the loss of protein, it failed to improve lung edema and pulmonary gas exchange, thereby limiting its clinical use.

Animals↗

Aerosol deposition in mechanically ventilated patients. Optimizing nebulizer delivery.

Previous studies have suggested that nebulizers are inefficient in delivering aerosolized medication to the lung in patients supported by mechanical ventilation. In a recent bench study, we characterized factors that may affect aerosol delivery, i.e., nebulizer type, ventilator settings (duty cycle), volume fill, and humidification as well as technical factors affecting measurement of deposition (e.g., radiolabeled compounds). Utilizing the predictions from our bench data, the present study was designed to assess nebulized aerosol delivery to ventilated patients under optimal conditions. Seven patients who were receiving mechanical ventilation (Bear II) via tracheostomy tube (TT) were studied. The humidifier was turned off. The test aerosol, a saline solution labeled with 99mTechnetium bound to human serum albumin (99mTc-HSA), was administered via a jet nebulizer (AeroTech II, 1.1 +/- 1.8 microns [mass median aerodynamic diameter, MMAD, geometric standard deviation, sigma g]), which was incorporated into the ventilator circuit and run to dryness. Inhaled and deposited radioactivity were measured by a mass balance/filter technique. TT versus lung deposition were quantified by removal of the inner cannula and direct measurement of TT deposition in a well counter. Inspiratory versus expiratory components of TT deposition were separated via bench techniques for each TT tube and breathing pattern. The regional distribution of deposited radioactivity was confirmed by gamma camera scans before and after TT removal. Measured radioactivity at each site was expressed as a percentage of nebulizer charge (i.e., the quantity of radioactivity originally placed in the nebulizer). On average, 30.6 +/- 6.3% (SD) of the charge was inhaled by the ventilated patients. Mean deposition in the TT during inspiration was 2.6 +/- 0.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Continuous versus intermittent nebulized terbutaline: plasma levels and effects.

The purpose of this investigation was to compare continuous versus intermittent nebulization of a beta 2-agonist, terbutaline, to determine whether differences exist in plasma concentrations or adverse cardiovascular effects of the drug with these two techniques for its administration. Sixteen children 6 to 16 yr of age, admitted for acute asthma, were enrolled in this randomized double-blind clinical trial. Nebulization of 16 mg of terbutaline over an 8-h period was performed either continuously or intermittently, with a dose of 4 mg given over 20 min every 2 h. The peak plasma terbutaline concentration for the intermittent nebulization treatment (INT) group (5.1 +/- 2.1 ng/ml) occurred 1 h after the fourth inhalation treatment and was similar to the peak concentration for the continuous nebulization treatment (CNT) group, which was reached at the end of the 8 h period (4.7 +/- 2.3 ng/ml). The maximum heart rate increase for the INT group (19.6 +/- 18.3 bpm) occurred 1 h after the fourth dose and was similar to the peak observed in the CNT group (19.6 +/- 19.2 bpm), which occurred after 3 h. Similar increases in systolic and decreases in diastolic pressures were observed for the INT and CNT groups. No evidence of serious adverse myocardial complications was seen in either group, as evidenced by measurements of the MB fraction of creatine phosphokinase (CPK-MB) and Holter-monitor recordings. Continuous nebulization of the terbutaline produces similar plasma concentrations and cardiovascular physiologic responses as intermittent nebulization.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗