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* From the Division of Pulmonary/Critical Care, Department of Medicine and Department of Preventive Medicine, Stony Brook University, Stony Brook, NY.
Correspondence to: Thomas G. O’Riordan, MD, Division of Pulmonary/Critical Care Medicine, HSC 17–040, Stony Brook University, Stony Brook, NY 11794-8172; e-mail: toriordan{at}notes.cc.sunysb.edu
Abstract
Objective: In vitro data suggest that the S-enantiomer of albuterol can induce mucociliary dysfunction. This clinical study assesses the clinical significance of standard doses of the S-enantiomer on airway secretions in long-term intubated patients by comparing a racemic formulation of albuterol, an R-enantiomer formulation, and normal saline solution.
Design: A placebo-controlled crossover study.
Patients: Fourteen stable intubated patients with a median duration of intubation of 21 months and a median age of 72 years.
Setting: Long-term ventilator unit in skilled nursing facility.
Interventions: Following a 2-week washout period during which regularly scheduled ß2-agonists were discontinued, tracheal aspirates were collected for 4 h/d for a 5-day period to establish baseline values, and the patients were then randomized in crossover manner to each of three nebulized treatments: normal saline solution, racemic albuterol, and R-albuterol. Each treatment was administered three times daily for 5 days, followed by a 2-day washout.
Measurements: Tracheal aspirates were analyzed for volume, sodium, chloride, bicarbonate, interleukin (IL)-8, IL-1ß, soluble intercellular adhesion molecule, and tumor necrosis factor-
.
Results: There were no consistent significant differences among the three treatment periods either in terms of volume of secretions or in the concentrations of the electrolytes or the inflammatory indexes. However, all three treatments, including saline solution, were associated with increased secretion volume after the first dose, but this effect was not apparent on subsequent doses.
Conclusion: There were no significant differences between racemic albuterol and R-albuterol observed in this study for any of the parameters studied, suggesting that the S-enantiomer does not adversely affect airway secretions at recommended doses. In addition, the routine administration of nebulized ß2-sympathomimetic agonists to stable patients undergoing prolonged intubation, for the sole purpose of changing the volume and composition of secretions of airway secretions, is not supported by the results of this study.
Key Words: albuterol • ß2-agonists • hypersecretion • levalbuterol • tracheobronchitis
Albuterol (salbutamol) is one of the most commonly prescribed short-acting ß2-agonists. For several decades, it has been administered as a racemic mixture of two enantiomers (R-albuterol and S-albuterol) The R-enantiomer interacts with the ß2-receptor and is responsible for the efficacy of the drug in treating bronchial obstruction in asthma and COPD as well as for predictable ß2-receptor–mediated side effects such as tachycardia, tremor, and hypokalemia.1 In contrast, the S-enantiomer does not interact with the ß2-receptor and thus does not contribute to efficacy or to the ß-receptor–mediated side effects described above. Since 1999, a single enantiomer proprietary formulation of R-albuterol has been available in the United States. Despite being more expensive that the generic racemic formulations, it has been prescribed in part because of concern that the S-enantiomer may potentially cause adverse effects through as yet undefined mechanisms other than the ß2-receptor.2345 For example, apropos the present study, in vitro data have suggested that the S-enantiomer can cause ciliary dysfunction and alterations in airway secretion.5 This is, we believe, the first clinical study to address the concern of whether the S-enantiomer of albuterol contributes to secretory dysfunction.
In contradistinction to the concerns about the S-enantiomer of albuterol causing secretory dysfunction, there is widespread "off-label" clinical use of ß2-sympathomimetic agents to enhance mucociliary clearance in patients with cystic fibrosis, chronic bronchitis, bronchiectasis, and tracheobronchitis associated with mechanical ventilation.6 The rationale for this use is based in part on in vitro data; these agents can increase ciliary beat frequency,5 alter the rate of secretion from cultures of bronchial cells and tracheobronchial explants,7 and modify electrolyte transport in epithelial cell cultures.89 Formal clinical evaluation of the mucociliary effects of these agents has consisted primarily of subjective symptom questionnaires10 or single-dose studies either of the clearance of radiolabeled mucus or of bronchoscopic/fluoroscopic measurements of the movement of tracheobronchial Teflon particles.611 However, one study12 of eight stable patients with bronchiectasis found that single nebulized doses of saline solution or terbutaline, when used as an adjunct to chest physical therapy, resulted in an increased yield of expectorated sputum when compared to chest physical therapy alone. While the terbutaline, but not the saline solution, also resulted in enhanced clearance of radiolabeled mucus as measured by 
scintigraphy, it was not clear if the observed effect on sputum yield was due to an effect of the ß2-agonist stimulation or to a nonspecific effect of increased hydration of secretions after nebulization therapy. One of the principal reasons for the dearth of clinical data on the effects of ß-agonists on airway secretions is that while the clinical manifestations of mucociliary dysfunction are obvious, there is no universally accepted method of objectively measuring secretory function. As a result, even a medication such as recombinant deoxyribonuclease I that was specifically designed to treat secretory dysfunction in cystic fibrosis, was approved by the US Food and Drug Administration based primarily on its objective impact on spirometry and the rate of acute exacerbations but with no clinical secretion data listed in the official prescribing information.13 Not surprisingly, therefore, the bronchodilator properties of ß-agonists have been precisely quantified, while the in vivo secretory properties remain largely unknown.
We have reported a promising approach in the evaluation of mucociliary dysfunction in patients receiving prolonged mechanical ventilation: the timed collection of tracheobronchial secretions to measure volume and to assess parameters of inflammation. Patients receiving prolonged mechanical ventilation acquire hypersecretion associated with bacterial colonization and neutrophilic inflammation (ventilator-associated tracheobronchitis).141516 The technique of timed secretion collection has been successfully used to assess the impact of systemic and aerosolized antibiotics in these patients. As a result of this antibiotic experience, we decided to invite a clinically stable cohort of patients in a long-term care facility to participate in what we believe is the first study that objectively evaluates the impact of ß2-sympathomimetic agonists on secretory function in patients receiving mechanical ventilation, with emphasis on whether the S-enantiomer of albuterol can affect airway secretions.
Materials and Methods
Study Design
This is a placebo-controlled crossover study. During a 2-week washout period, regularly scheduled ß2-agonists were discontinued. Patients then underwent daily measurements of secretion volume for 1 week with no aerosolized medications. The patients then received a series of three nebulized treatments in random order during consecutive weeks: normal saline solution, generic racemic albuterol, and R-albuterol. The racemic albuterol and R-albuterol were supplied by the manufacturers as premixed unit-dose vials, and no additional diluent was added for this study. The formulations of racemic albuterol and R-albuterol were both preservative free.
The primary comparison was the weekly cumulative volume of secretions under each of the three treatments vs the control secretion volume. Cumulative weekly secretion volume for the purposes of the study is defined as the aggregate of five consecutive, daily, 4-h collections of tracheal aspirates. The secondary end points for the study were the cumulative weekly volume of secretion for the first hour of the 4-h collection period, the daily 1-h and 4-h secretion volume, as well as electrolyte and cytokine concentrations in tracheal secretions.
Patients
Seventeen patients in a skilled nursing home ventilator unit were enrolled. To qualify for the study, patients had to be undergoing daily mechanical ventilation via a tracheostomy or have a tracheostomy associated with prior mechanical ventilation but in whom the decannulation had been deferred due to hypersecretion. Twenty-nine patients in the unit were assessed for participation in the study. Two patients with COPD were considered ineligible because of frequent bronchospasm and the need for frequent bronchodilator treatments. Another was considered ineligible because of unstable coronary artery disease, and nine patients declined the opportunity to participate. Of the 17 patients who commenced the study, 3 were withdrawn during the washout phase: 1 patient was observed to have an episode of aspiration of gastric contents requiring antibiotic therapy, and 2 others withdrew consent. None of these patients withdrew because of a need for frequent ß2-agonist therapy. Analyzable data were obtained from the remaining 14 patients: 13 patients who completed therapy with all study treatment groups and 1 patient (patient 8) who was withdrawn after 1 week of one treatment (albuterol) and 1 day of another treatment (saline solution) because an infected gastrostomy site that required antibiotics. Their demographics are summarized in Table 1 . For patients 10, we included the electrolyte and cytokine data from the supernatant of the single day of saline solution therapy but did not include this single-day data point in the analysis of secretion volume. At entry to washout period, patients were changed to R-albuterol, 1.25 mg q8h, as needed, and other ß2-agonists and ipratropium orders were discontinued. Patients who were receiving an inhaled corticosteroid (one patient), systemic corticosteroids (two patients), or a ß-sympathomimetic antagonist (one patient) were continued on these medications.
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Bench-Testing Estimate of Aerosol Delivery
Before proceeding to the clinical trial, a previously described model of aerosol delivery through a mechanical ventilator was used to estimate the amount of medication that these patients would be likely to inhale.171819 The model, which is shown in Figure 1
, incorporated the same type of ventilator (T Bird Ventilator; Viasys; Conshohocken, PA) and tubing that was to be used in the clinical study together with a test lung (Vent-Aid TTL; MI Instruments; Grand Rapids, MI) and an inline monitor of ventilator performance (CP 100 Monitor; Bicore; Irvine, CA). A nebulizer (AeroTech II; CIS-US; Bedford, MA) was placed distal to the Y-piece, and aerosol was generated throughout the respiratory cycle using an external source of compressed air (8 L/min, 50 pounds per square inch). The heat and moisture exchange filter was removed from the circuit during nebulization. The nebulizer was charged with 3 mL of racemic albuterol mixed with a radioaerosol tracer, technetium pertechnetate (99mTc). Radioactivity was collected on a low-resistance paper filter placed at the distal end of a tracheostomy tube (inner diameter, 6.0 mm). The radioactivity on the filter was measured in a dose calibrator (CRC; Capintec; Pittsburgh, PA); after being corrected for decay time, it was expressed as a percentage of the radioactivity placed in the nebulizer. This type of bench testing has been shown to have useful predictive value for subsequent clinical deposition studies,1819 and it has shown that there is good correlation between the radiotracer and an albuterol assay.17 The nebulizer was interposed between the Y-piece and the tracheostomy tube. The "flow-by" bias flow rate was set at 10 L/min, the breathing rate was set at 15 breaths/min, and the tidal volume was 750 mL with an inspiratory/expiratory ratio of 1:1. In both the bench model and the clinical study, nebulization occurred at constant flow throughout the respiratory cycle. The model predicted that approximately 11.0% of dose placed in nebulizer would be delivered to the distal end of the tracheostomy tube.
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For a 2-week washout period, no regularly scheduled aerosolized bronchodilators were prescribed. No patient required a rescue nebulizer treatment (R-albuterol, 1.25 mg q8h as needed, had been ordered) during this period of time or during any of the study treatments. Following this 2-week washout period, secretions were collected over 4 consecutive weeks: the first week was designated as the control period with no nebulized treatments followed by 3 treatment weeks consisting of 1 week of R-albuterol, 1.25 mg/3 mL tid, 1 week of racemic albuterol, 2.5 mg/3 mL tid, and 1 week of normal saline solution, 3 mL tid, with the order of treatments being random. During the treatment weeks, nebulized treatments were delivered Monday to Friday, and scheduled at 8 AM, 2 PM, and 10 PM. Each intervening weekend served as a 2-day washout period with no scheduled treatments. Patients were suctioned for 30 to 60 s without the addition of exogenous saline solution as previously described.15 A plastic catheter (Kendall 14F; Tyco Health Care; Mansfield, MA) was inserted gently in to the airway until resistance was encountered and then withdrawn slowly with intermittent suctioning (120 cm H2O pressure) until secretions were cleared. Prior to the 8 AM treatment, patients were suctioned and these secretions were discarded. Timed 4-h collection of secretion began immediately after completion of the 8 AM nebulization of study medication. The volume of secretions during this 4-h period was recorded after 1 h and after 4 h. At a minimum, all patients were suctioned after 1 h and 4 h, but some patients required more frequent suctioning and the volumes acquired by this additional suctioning were added to the 1-h and 4-h totals as appropriate For the purposes of analysis and presentation, five daily, timed 4-h volume measurements were added together to provide a single data point for an individual subject receiving a specific treatment. The data from the 5-day aggregate of the first-hour volume measurements were analyzed separately from the 4-h volume data to make sure that an "immediate" treatment effect would be detectable. This collection method reflects both mucociliary and cough clearance.
On collection, specimens were placed in an ice-filled container to minimize autolysis and stored at – 10°C. The aspirate was ultracentrifuged at 45,000 revolutions per minute for 1.5 h at 4°C to separate the sol and gel phases. The supernatant (sol phase) was carefully aspirated and stored at – 10°C until analyzed.
Electrolyte Measurement
Electrolytes (sodium, chloride, and bicarbonate) were measured in the supernatants by a hospital reference laboratory using ion-selective electrolysis (Hitachi Modular System; Tokyo, Japan). The samples used for electrolyte measurements were the supernatants of pooled specimens collected over 5 days as described above.
Cytokine Assays
Inflammatory parameters studied were the cytokines interleukin (IL)-1ß, tumor necrosis factor (TNF)-, and IL-8 and the adhesion molecule serum intracellular adhesion molecule-1 (sICAM). sICAM and IL-8 were studied as indexes of neutrophil adhesion and chemotactic activity, respectively. IL-1ß, and TNF- were studied as indexes of macrophage activation in the present study. IL-1ß, IL-8, and TNF- were measured using quantitative sandwich immunoassay kits (R&D Systems; Minneapolis, MN) and assays were performed in accordance with the instructions of the manufacturer. Sol samples were assayed by enzyme-linked immunosorbent assay technique using a 96-microwell plate with a specific antibody against the cytokine being tested that was adsorbed to the wells. Standards and samples were added and the immobilized antibody bound any cytokine present. After washing to remove unbound substances, peroxidase-conjugated antibody against the cytokine that was bound to the primary antibody was added to wells. After washing to remove unbound antibody enzyme reagent, a substrate was added to the wells and color developed in proportion to the amount of cytokine present. The color development was stopped, and the intensity of the color measured by spectrophotometry (wavelength of 450 nm). A standard curve with an R value > 0.98 was used to calculate cytokine levels.
Statistical Analysis
The primary outcome was the volume of weekly 4-h secretion under different treatments (ie, the cumulative totals of five consecutive 4-h collections). To normalize differences in baseline secretion volume, the control value with no treatment for each patient was subtracted from the values for each treatment. The following secondary outcomes were studied: weekly 1-h volumes, daily 1-h and 4-h secretion volumes, as well as weekly measurements of sodium, chloride and bicarbonate, sICAM, TNF-, IL-1ß, and IL-8 concentration in secretions. Due to the cross-over design of this study, which results in repeated measurements data, linear mixed effects models20 were used to compare the treatment effects, adjusting for important covariates, such as gender, diagnosis (cardiopulmonary vs neurologic), prior ß-agonist usage status, age, and duration of intubation. A p value of 0.05 was regarded as statistically significant.
Results
In Figure 2 , the data from individual subjects are illustrated with each set of four bar graphs representing the sum of 5 days of aspirate volumes for the control period and each of the three treatment periods. Each data point in Figure 2, top, a, and bottom, b, represents the sum of five individual timed daily volume measurements. Figure 2, top, a, presents data for the 5-day aggregate of first-hour volumes, while Figure 2, bottom, b, presents the 5-day aggregate volumes at 4 h. Table 2 shows mean values for the 5-day aggregate of the first-hour volume measurements and for the 5-day aggregate of 4-h volume measurements. After normalizing for baseline volume value (under no treatment), the three treatment groups (saline solution, racemic albuterol, and R-albuterol) showed no differential treatment effect for the primary end point of aggregate 4-h tracheal aspirate volumes obtained on 5 consecutive days (p = 0.84), nor was there any effect seen on 4-h secretion volume measured on a daily basis (p = 0.91).
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Mean concentrations of electrolytes (sodium, chloride, and bicarbonate) are illustrated in Figure 3 . There are no significant differences between the treatment groups (p = 0.44, p = 0.51, p = 0.84, respectively). Similarly the mean data for inflammatory indexes (cytokines IL-8, IL-1, and TNF, as well as sICAM), which are shown in Table 3 , also reveal no significant treatment differences (p = 0.69, p = 0.35, p = 0.12, p = 0.99, respectively). No adverse events were noted in the study that could be attributed to any of the study medications.
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This is the first clinical study to compare the effects of a racemic and a single-enantiomer formulation on airway secretion in any population, and the first study to objectively evaluate the impact of ß2-sympathomimetic agonists on secretory function in tracheostomized patients receiving mechanical ventilation, and only the second study of the effects of these agents on secretion volume. We report that all treatments, including saline solution, were associated with a transient increase in secretion volume in the first hour following the first dose of nebulized treatment. This is consistent with the observation by Sutton et al12 that both nebulized terbutaline and saline solution increased volume of expectorated sputum in patients with bronchiectasis, emphasizing the importance of a control aerosol in studies of secretory dysfunction. However, there were no significant treatment-related differences among the three treatments on any of the parameters. The observation that there was no difference between racemic albuterol and R-albuterol indicates that at approved doses, the S-enantiomer does not appear to have clinically significant adverse effects on mucociliary function.
Before extrapolating from our findings to potential clinical implications, it is important to outline the strengths and limitations of the study design. This method of timed tracheal aspirate collection over a 5-day period (collected without exogenous saline solution) has been shown to be capable of detecting clinically significant decreases in the volume of secretions with aerosolized and systemic antibiotics in patients who produce 
2 mL of secretions over a 4-h period.1516 For example, after 14 to 21 days of aerosolized gentamicin (nine courses of treatments in six patients), the volume of secretions (mean ± SD of five 4-h collections) decreased from 7.4 ± 1.7 to 3.6 ± 1.7 mL, with every patient showing a decrease in volume.16 From these prior studies, we have found that the collection of specimens for 4 h/d over a 5-day period is sufficient to control for intrasubject variability in secretion volume. To control for the marked intersubject variability in volumes, a crossover design is essential for the completion of the study at a single site. The crossover design enables each subject to serve as his/her own control. This allows more meaningful comparison between various treatments. However for a crossover design to be utilized, it is necessary that the patients be relatively clinically stable over a period of several weeks. From our prior experience,1516 the most important confounding variables in secretion measurement are the development of new respiratory tract infections and the introduction of antibiotics, two events that frequently complicate the course of patients receiving mechanical ventilation in the setting of an ICU. The stability of the current study population is supported by the observation that even though each individual patient had to undergo a total of 40 measurements of secretion volume over a period of 80 h of secretion collection in a 4-week period to complete the protocol, (in addition to remaining stable during a preceding 2-week washout phase from ß2-agonists), only two patients in the present study had to be withdrawn because of the introduction of antibiotic therapy.
Other qualifications in interpreting the findings of this study relate to the delivered dose and the absence of bronchospasm in the study population. Doses of racemic albuterol and R-albuterol at the higher end of the approved dosing ranges were prescribed in the present study. The bench model used to calculate the delivered dose has been validated in a clinical study,19 and thus we can reliably estimate that in current study, an average of 275 µg of albuterol reached the distal of the tracheostomy tube, a dose that can decrease airway resistance in intubated patients with obstruction.21 Because of the optimization of the aerosol delivery protocol in the present study (a high-performance nebulizer and absence of humidification were the main factors), these patients probably received a two- to three-times higher dose than is delivered to the airways of intubated patients in routine clinical practice in stable patients. The lung dose received by the patients in the present study is likely to be either greater than the inhaled doses in published studies that demonstrated an increase in mucociliary clearance with albuterol,622 or at least clinically equivalent to the dose of nebulized terbutaline that was reported to increase sputum yield12 (nebulized terbutaline is usually prescribed at double the nominal dose of albuterol).23
The absence of significant bronchospasm enabled the use of both control (no aerosol) and placebo (saline solution) treatment options in the present study, as well as a 2-week washout period from ß2-agonists. While these inactive treatment arms serve to make our findings more statistically robust, a design that excludes patients with bronchospasm means that the findings of the present may not apply to patients intubated acutely for asthma because of both differences in delivered dose and differences in airway mucociliary pathology. Patients intubated for status asthmaticus require much high doses of inhaled ß2-agonists, not only because nonoptimized aerosol delivery systems can be inefficient in the setting of mechanical ventilation, but more importantly because the airways become significantly more resistant to bronchodilators during status asthmaticus. Furthermore, our previous study24 has shown that mucociliary function is acutely dysfunctional in patients during status asthmaticus, a phenomenon that improves markedly over the following weeks, and this acute mucociliary dysfunction could theoretically respond differently to ß-agonists compared to the airways of stable patients. At clinically recommended doses, the S-enantiomer does not appear to have adverse effects on mucociliary clearance, as evidenced by the lack of difference between the two formulations of albuterol in the present study. However, as the approved doses are usually exceeded several fold in patients with status asthmaticus and because the S-enantiomer is not metabolized by the same pathway as the R-enantiomer, the S-enantiomer tends to accumulate faster the R-enantiomer with repeated administration,25 and further studies may be required in that population to determine if secretions are affected.
We are not aware of any published radioaerosol clearance studies in intubated patients. However, radioaerosol and roentgenographic Teflon particle studies61122 demonstrate an increase rate of mucociliary clearance and tracheal mucous velocity after administration either systemic ß2-agonists or inhaled ß2-agonists in normal volunteers, and patients with COPD, asthma, and bronchiectasis, and to a lesser extent in cystic fibrosis. However, some investigators27 have reported that a single doses of salbutamol (albuterol) does not effect radioaerosol clearance in stable asthma26 and COPD. The effects of steady-state ß2-agonist therapy (which is more comparable to the present study protocol) have been assessed in two studies. Perry and Smaldone28 reported no significant effect of maintenance therapy with inhaled short-acting ß2-agonists, inhaled corticosteroids, and oral theophylline on mucociliary clearance in normal subjects over a 7-day period. In contrast, a study of the effects of 2 weeks of treatment with the long-acting ß2-agonist salmeterol revealed a subtle increase in mucociliary clearance in patients with stable asthma.29 Comparative studies on the affects of racemic vs single enantiomer of albuterol on radiolabeled clearance have not been published.
The data from this study may be of value in the design of future studies in at least five ways. Firstly, our data may serve as a guideline for sample-size calculation for a study of an unstable group of patients (eg, acute ICU patients without bronchospasm), which would require a parallel-group design rather than a crossover design. The current study had a statistical power of 74% of detecting a clinically significant difference of 2 mL/d between an active medication and saline solution in 4-h volume measurements, at an level of 0.05.30 With the reported level of between-subject variability, a study sample of 48 patients per group would be needed to achieve the same level of statistical power in the absence of the crossover design. Secondly, our observation of an association between an increase in volume with the first dose of all treatments suggests that a saline solution control would be desirable for these studies. Thirdly, measurements taken after day 1 would appear to be needed for clinical relevance. The data indicate that measurements on days 2 to 5 are similar so that a 5-day collection may not be needed. Fourthly, in future studies of short acting ß-agonists, a 1-h time collection may be preferable to a 4-h collection not only in terms of convenience but because there is also a trend in our data that it may be more sensitive indicator of response than a more prolonged collection.
Measurements of volume are subject to the question as to whether an intervention that increases clearance of secretions is "good," implying that the intervention is facilitating the removal of secreted, stagnant secretions from the airway, or "bad," implying that the intervention is further stimulating goblet cells or submucosal glands to synthesize or secrete more mucus. In the present study, our intervention had no clinically detectable effect on volume, so no beneficial or deleterious effect on this parameter need be hypothesized. Although the lack of a clinically significant effect on secretion volume does not support ß2-agonist enhancement of clearance of secretions in this population, it should also be stated that these data do not suggest that ß2-agonists, and in particular the S-enantiomer of albuterol, are potentially harmful secretagogues in these stable, long-term intubated tracheostomized patients.
In the present study, there were no significant treatment differences in sodium, chloride, and bicarbonate levels in the supernatant of the tracheal aspirates with normal saline solution, the racemic mixture, or the R-enantiomer of albuterol. Electrolyte concentrations in patients receiving prolonged mechanical ventilation have not been previously published. However, a wide range of electrolyte values has been reported in published studies83132 of tracheobronchial secretions from patients with cystic fibrosis, laryngectomized patients, and electively intubated normal volunteers. Most of the differences in published electrolyte levels between studies are likely to reflect differences in hydration related to specimen acquisition and preparation. Compared with the laboratory normograms for serum electrolytes, tracheal aspirate levels of chloride were consistently elevated, a finding consistent with previous investigators. Bicarbonate levels were consistently reduced, but relevant comparator data for this electrolyte have not been published.
As in previous studies1516 in intubated patients, there is wide intersubject variability in cytokine studies reflective of the heterogeneous and poorly understood pathophysiology of this patient population, but there was no evidence of ß2-agonist treatment effect. In the prior studies,1516 average levels of cytokines in patients receiving long-term ventilation were elevated to levels similar to those reported in patients with cystic fibrosis. Intubated patients have abnormal secretions with neutrophils as the dominant cell type, although the volume and degree of purulence varies.33 The S-enantiomer did not appear to be proinflammatory using these indexes.
In conclusion, there were no significant differences between racemic albuterol and R-albuterol observed in this study for any of the parameters studied, suggesting that the S-enantiomer does not adversely affect airway secretions at recommended doses. In addition, the routine administration of nebulized ß2-sympathomimetic agonists to stable patients undergoing prolonged intubation for the sole purpose of changing the volume and composition of secretions of airway secretions is not supported by the results of this study. These data may be useful for the design of future studies of other intubated patient populations.
Acknowledgements
We thank the Respiratory Care Department staff and the nursing staff of Floor Four East, Gurwin Jewish Geriatric Center, Commack, NY, for their cooperation with the study. We thank Teresa Kramer, RN, ANP, April Plank, RN, ANP, and Barbara Starke, RN, ANP, for the specimen collection. We thank Mohammed Amin, MD, and Akbar Shah, MD, for performing the ventilator bench testing, and Mr. Robert Perry for performing the cytokine assays.
Footnotes
Abbreviations: IL = interleukin; sICAM = serum intracellular adhesion molecule-1; TNF = tumor necrosis factor
This study was supported by a grant from Sepracor Inc., Marlborough, MA.
Received for publication May 2, 2005. Accepted for publication October 1, 2005.
References
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