Association of dyspnoea, mortality and resource use in hospitalised patients.

As many as one in 10 patients experience dyspnoea at hospital admission but the relationship between dyspnoea and patient outcomes is unknown. We sought to determine whether dyspnoea on admission predicts outcomes.We conducted a retrospective cohort study in a single, academic medical centre. We analysed 67 362 consecutive hospital admissions with available data on dyspnoea, pain and outcomes. As part of the Initial Patient Assessment by nurses, patients rated "breathing discomfort" using a 0 to 10 scale (10="unbearable"). Patients reported dyspnoea at the time of admission and recalled dyspnoea experienced in the 24 h prior to admission. Outcomes included in-hospital mortality, 2-year mortality, length of stay, need for rapid response system activation, transfer to the intensive care unit, discharge to extended care, and 7- and 30-day all-cause readmission to the same institution.Patients who reported any dyspnoea were at an increased risk of death during that hospital stay; the greater the dyspnoea, the greater the risk of death (dyspnoea 0: 0.8% in-hospital mortality; dyspnoea 1-3: 2.5% in-hospital mortality; dyspnoea ≥4: 3.7% in-hospital mortality; p<0.001). After adjustment for patient comorbidities, demographics and severity of illness, increasing dyspnoea remained associated with inpatient mortality (dyspnoea 1-3: adjusted OR 2.1, 95% CI 1.7-2.6; dyspnoea ≥4: adjusted OR 3.1, 95% CI 2.4-3.9). Pain did not predict increased mortality. Patients reporting dyspnoea also used more hospital resources, were more likely to be readmitted and were at increased risk of death within 2 years (dyspnoea 1-3: adjusted hazard ratio 1.5, 95% CI 1.3-1.6; dyspnoea ≥4: adjusted hazard ratio 1.7, 95% CI 1.5-1.8).We found that dyspnoea of any rating was associated with an increased risk of death. Dyspnoea ratings can be rapidly collected by nursing staff, which may allow for better monitoring or interventions that could reduce mortality and morbidity.

Controlled Delivery of 80 mg Aerosol Furosemide Does Not Achieve Consistent Dyspnea Relief in Patients.

PURPOSE: Aerosol furosemide may be an option to treat refractory dyspnea, though doses, methods of delivery, and outcomes have been variable. We hypothesized that controlled delivery of high dose aerosol furosemide would reduce variability of dyspnea relief in patients with underlying pulmonary disease. METHODS: Seventeen patients with chronic exertional dyspnea were recruited. Patients rated recently recalled breathing discomfort on a numerical rating scale (NRS) and the multidimensional dyspnea profile (MDP). They then performed graded exercise using an arm-ergometer. The NRS was completed following each exercise grade, and the MDP was repeated after a pre-defined dyspnea threshold was reached. During separate visits, patients received either aerosol saline or 80 mg of aerosol furosemide in a randomized, double-blind, crossover design. After treatment, graded exercise to the pre-treatment level was repeated, followed by completion of the NRS and MDP. Treatment effect was defined as the difference between pre- and post-treatment NRS at end exercise, expressed in absolute terms as % Full Scale. "Responders" were defined as those showing treatment effect ≥ 20% of full scale. RESULTS: Final analysis included 15 patients. Neither treatment produced a statistically significant change in NRS and there was no significant difference between treatments (p = 0.45). There were four "responders" and one patient whose dyspnea worsened with furosemide; two patients were responders with saline, of whom one also responded to furosemide. No adverse events were reported. CONCLUSIONS: High dose controlled delivery aerosol furosemide was not statistically different from saline placebo at reducing exercise-induced dyspnea. However, a clinically meaningful improvement was noted in some patients.

Multidimensional Dyspnea Profile: an instrument for clinical and laboratory research.

There is growing awareness that dyspnoea, like pain, is a multidimensional experience, but measurement instruments have not kept pace. The Multidimensional Dyspnea Profile (MDP) assesses overall breathing discomfort, sensory qualities, and emotional responses in laboratory and clinical settings. Here we provide the MDP, review published evidence regarding its measurement properties and discuss its use and interpretation. The MDP assesses dyspnoea during a specific time or a particular activity (focus period) and is designed to examine individual items that are theoretically aligned with separate mechanisms. In contrast, other multidimensional dyspnoea scales assess recalled recent dyspnoea over a period of days using aggregate scores. Previous psychophysical and psychometric studies using the MDP show that: 1) subjects exposed to different laboratory stimuli could discriminate between air hunger and work/effort sensation, and found air hunger more unpleasant; 2) the MDP immediate unpleasantness scale (A1) was convergent with common dyspnoea scales; 3) in emergency department patients, two domains were distinguished (immediate perception, emotional response); 4) test-retest reliability over hours was high; 5) the instrument responded to opioid treatment of experimental dyspnoea and to clinical improvement; 6) convergent validity with common instruments was good; and 7) items responded differently from one another as predicted for multiple dimensions.

Arterial stiffness, oxidative stress, and smoke exposure in wildland firefighters.

OBJECTIVES: To assess the association between exposure, oxidative stress, symptoms, and cardiorespiratory function in wildland firefighters. METHODS: We studied two Interagency Hotshot Crews with questionnaires, pulse wave analysis for arterial stiffness, spirometry, urinary 8-iso-prostaglandin F2α (8-isoprostane) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and the smoke exposure marker (urinary levoglucosan). Arterial stiffness was assessed by examining levels of the aortic augmentation index, expressed as a percentage. An oxidative stress score comprising the average of z-scores created for 8-OHdG and 8-isoprostane was calculated. RESULTS: Mean augmentation index % was higher for participants with higher oxidative stress scores after adjusting for smoking status. Specifically for every one unit increase in oxidative stress score the augmentation index % increased 10.5% (95% CI: 2.5, 18.5%). Higher mean lower respiratory symptom score was associated with lower percent predicted forced expiratory volume in one second/forced vital capacity. CONCLUSIONS: Biomarkers of oxidative stress may serve as indicators of arterial stiffness in wildland firefighters.

Dyspnea affective response: comparing COPD patients with healthy volunteers and laboratory model with activities of daily living.

BACKGROUND: Laboratory-induced dyspnea (breathing discomfort) in healthy subjects is widely used to study perceptual mechanisms, yet the relationship between laboratory-induced dyspnea in healthy volunteers and spontaneous dyspnea in patients with chronic lung disease is not well established. We compared affective responses to dyspnea 1) in COPD patients vs. healthy volunteers (HV) undergoing the same laboratory stimulus; 2) in COPD during laboratory dyspnea vs. during activities of daily living (ADL). METHODS: We induced moderate and high dyspnea levels in 13 COPD patients and 12 HV by increasing end-tidal CO2 (PETCO2) during restricted ventilation, evoking air hunger. We used the multidimensional dyspnea profile (MDP) to measure intensity of sensory qualities (e.g., air hunger (AH) and work/effort (W/E)) as well as immediate discomfort (A1) and secondary emotions (A2). Ten of the COPD subjects also completed the MDP outside the laboratory following dyspnea evoked by ADL. RESULTS: COPD patients and HV reported similar levels of immediate discomfort relative to sensory intensity. COPD patients and HV reported anxiety and frustration during laboratory-induced dyspnea; variation among individuals far outweighed the small differences between subject groups. COPD patients reported similar intensities of sensory qualities, discomfort, and emotions during ADL vs. during moderate laboratory dyspnea. Patients with COPD described limiting ADL to avoid greater dyspnea. CONCLUSIONS: In this pilot study, we found no evidence that a history of COPD alters the affective response to laboratory-induced dyspnea, and no difference in affective response between dyspnea evoked by this laboratory model and dyspnea evoked by ADL.

Dynamic expiratory tracheal collapse in morbidly obese COPD patients.

Morbid obesity may influence several aspects of airway function. However, the effect of morbid obesity on expiratory tracheal collapse in COPD patients is unknown. We thus prospectively studied 100 COPD patients who underwent full pulmonary function tests (PFTs), 6-minute walk test (6MWT), Saint George's Respiratory Questionnaire (SGRQ), and low-dose CT at total lung capacity and during dynamic exhalation with spirometric monitoring. We examined correlations between percentage dynamic expiratory tracheal collapse and body mass index (BMI). The association between tracheal collapse and BMI was compared to a control group of 53 volunteers without COPD. Patients included 48 women and 52 men with mean age 65 ± 7 years; BMI 30 ± 6; FEV1 64 ± 22% predicted and percentage expiratory collapse 59 ± 19%. Expiratory collapse was significantly associated with BMI (69 ± 12% tracheal collapse among 20 morbidly obese patients with BMI ≥ 35 compared to 57 ± 19% in others, p = 0.002, t-test). In contrast, there was no significant difference in collapse between healthy volunteers with BMI ≥ 35 and < 35. COPD patients with BMI ≥ 35 also demonstrated shorter 6MWT distances (340 ± 139 m vs. 430 ± 139 m, p = 0.003) and higher (worse) total SGRQ scores (48 ± 19 vs. 36 ± 20, p = 0.013) compared to those with BMI < 35. In light of these results, clinicians should consider evaluating for excessive expiratory tracheal collapse when confronted with a morbidly obese COPD patient with greater quality of life impairment and worse exercise performance than expected based on functional measures.

Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response.

RATIONALE: Opioids are commonly used to relieve dyspnea, but clinical data are mixed and practice varies widely. OBJECTIVES: Evaluate the effect of morphine on dyspnea and ventilatory drive under well-controlled laboratory conditions. METHODS: Six healthy volunteers received morphine (0.07 mg/kg) and placebo intravenously on separate days (randomized, blinded). We measured two responses to a CO(2) stimulus: (1) perceptual response (breathing discomfort; described by subjects as "air hunger") induced by increasing partial pressure of end-tidal carbon dioxide (Pet(CO2)) during restricted ventilation, measured with a visual analog scale (range, "neutral" to "intolerable"); and (2) ventilatory response, measured in separate trials during unrestricted breathing. MEASUREMENTS AND MAIN RESULTS: We determined the Pet(CO2) that produced a 60% breathing discomfort rating in each subject before morphine (median, 8.5 mm Hg above resting Pet(CO2)). At the same Pet(CO2) after morphine administration, median breathing discomfort was reduced by 65% of its pretreatment value; P < 0.001. Ventilation fell 28% at the same Pet(CO2); P < 0.01. The effect of morphine on breathing discomfort was not significantly correlated with the effect on ventilatory response. Placebo had no effect. CONCLUSIONS: (1) A moderate morphine dose produced substantial relief of laboratory dyspnea, with a smaller reduction of ventilation. (2) In contrast to an earlier laboratory model of breathing effort, this laboratory model of air hunger established a highly significant treatment effect consistent in magnitude with clinical studies of opioids. Laboratory studies require fewer subjects and enable physiological measurements that are difficult to make in a clinical setting. Within-subject comparison of the response to carefully controlled laboratory stimuli can be an efficient means to optimize treatments before clinical trials.

Mechanical ventilation guided by esophageal pressure in acute lung injury.

BACKGROUND: Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); however, the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention. METHODS: We randomly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure-guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). The primary end point was improvement in oxygenation. The secondary end points included respiratory-system compliance and patient outcomes. RESULTS: The study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure-guided group than in the control group (95% confidence interval, 78.1 to 98.3; P=0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P=0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure-guided group (P=0.01 by repeated-measures analysis of variance). CONCLUSIONS: As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)

Effectiveness of the VOICES/VOCES sexually transmitted disease/human immunodeficiency virus prevention intervention when administered by health department staff: does it work in the "real world"?

BACKGROUND: Prevention providers wonder whether benefits achieved in the original, researcher-led, efficacy trials of interventions are replicated when the intervention is delivered in real-world settings by their agency's staff. METHODS: A replication study was conducted at 2 public sexually transmitted disease (STD) clinics (New York City and San Juan, PR). Using a controlled trial design, intervention (VOICES/VOCES) and comparison conditions (regular clinic services) were assigned in alternating 4-week blocks. Trained agency staff delivered the intervention. Effectiveness was assessed for incident STDs, redemption of coupons for condoms at neighborhood location after the visit, and improved knowledge and attitudes about STDs and condoms. RESULTS: A total of 3365 patients were recruited, completed the protocol, and followed through STD surveillance systems for an average of 17 months. Of 397 with an incident infection, 226 (13.4%) were among those enrolled during comparison blocks; 171 were among those in the intervention condition (10.2%). Controlling for site and gender, participants enrolled during intervention blocks were significantly less likely to have an incident STD reported to the surveillance system (hazard ratio, 0.78; 95% confidence interval, 0.64-0.96). Intervention block participants scored higher on scales of STD knowledge (4.89 vs. 3.87, P < 0.001) and condom knowledge, attitude, and efficacy (10.98 vs. 9.16, P < 0.001). More of those exposed to VOICES/VOCES redeemed condoms (P < 0.05). Positive effects were more consistent in New York, which may be related to fidelity of implementation. CONCLUSIONS: A packaged human immunodeficiency virus prevention intervention can be delivered by agencies, with benefits similar to those achieved in the research setting.

Bronchial collapsibility at forced expiration in healthy volunteers: assessment with multidetector CT.

PURPOSE: To assess forced-expiratory bronchial collapsibility in healthy volunteers by using multidetector computed tomography (CT) and to compare the results with the current diagnostic criterion for bronchomalacia. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant study. Following informed consent, 51 healthy volunteers with normal pulmonary function and no history of smoking were imaged by using a 64-detector row scanner with spirometric monitoring at total lung capacity and during forced exhalation. The total study population (in whom both main bronchi were imaged) included 25 men and 26 women (mean age, 50 years). Each scan was analyzed at a workstation by a fellowship-trained thoracic radiologist. Cross-sectional area measurements were obtained from end-inspiratory and forced-expiratory CT images for the right main bronchus (RMB), left main bronchus, (LMB), and bronchus intermedius (BI), and the mean percentage of expiratory collapse was calculated for each bronchus. The number of participants who exceeded the current diagnostic threshold level (>50% expiratory reduction in cross-sectional area) for bronchomalacia was calculated. Comparisons of airway dimensions and airway collapse according to bronchial segment and sex were made by using repeated-measures analysis of variance. RESULTS: Mean percentage of expiratory collapse was 66.9% ± 19.0 (standard deviation) for the RMB and 61.4% ± 16.7 for the LMB. Thirty-seven (73%) of 51 participants exceeded the diagnostic threshold level for bronchomalacia. Significant differences were observed in mean percentage of expiratory collapse between the RMB (66.9% ± 19.0) and LMB (61.4% ± 16.7) (P = .0005). Among a subgroup of 37 participants in whom the BI was also imaged, the mean percentage of expiratory collapse was 61.8% ± 22.8, and 27 (73%) participants exceeded the diagnostic threshold level for bronchomalacia. CONCLUSION: Healthy volunteers demonstrate a wide range of forced-expiratory bronchial collapse, frequently exceeding the current diagnostic threshold level for bronchomalacia.

Tracheal collapsibility in healthy volunteers during forced expiration: assessment with multidetector CT.

PURPOSE: To assess forced expiratory tracheal collapsibility in healthy volunteers by using multidetector computed tomography and to compare the results with the current diagnostic criterion for tracheomalacia. MATERIALS AND METHODS: An institutional review board approved this HIPAA-compliant study. After informed consent was obtained, 51 healthy volunteers (age range, 25-75 years) with normal spirometry results and no history of smoking or risk factors for tracheomalacia were prospectively studied. Volunteers were imaged with a 64-detector row scanner, with spirometric monitoring at total lung capacity and during forced exhalation, with 40 mAs, 120 kVp, and 0.625-mm detector collimation. Cross-sectional area and sagittal and coronal diameters of the trachea were measured 1 cm above the aortic arch and 1 cm above the carina. The percentage of expiratory collapse, the reduction in sagittal and coronal diameters, and the number of participants exceeding the current diagnostic criterion (>50% expiratory reduction in cross-sectional area) for tracheomalacia were calculated. RESULTS: The final study population included 25 men and 26 women (mean age, 50 years). The mean percentage of expiratory reduction in tracheal lumen cross-sectional area was 54.34% +/- 18.6 (standard deviation) in the upper trachea and 56.14% +/- 19.3 in the lower trachea. Forty (78%) participants exceeded the current diagnostic criterion for tracheomalacia in the upper and/or lower trachea. Decreases in cross-sectional area of the upper and lower trachea correlated well with decreases in sagittal (r = 0.807 and 0.688, respectively) and coronal (r = 0.779 and 0.751, respectively) diameters (P < .001 for each correlation). CONCLUSION: Healthy volunteers demonstrate a wide range of forced expiratory tracheal collapse, frequently exceeding the current diagnostic criterion for tracheomalacia.

Effect of a brief video intervention on incident infection among patients attending sexually transmitted disease clinics.

BACKGROUND: Sexually transmitted disease (STD) prevention remains a public health priority. Simple, practical interventions to reduce STD incidence that can be easily and inexpensively administered in high-volume clinical settings are needed. We evaluated whether a brief video, which contained STD prevention messages targeted to all patients in the waiting room, reduced acquisition of new infections after that clinic visit. METHODS AND FINDINGS: In a controlled trial among patients attending three publicly funded STD clinics (one in each of three US cities) from December 2003 to August 2005, all patients (n = 38,635) were systematically assigned to either a theory-based 23-min video depicting couples overcoming barriers to safer sexual behaviors, or the standard waiting room environment. Condition assignment alternated every 4 wk and was determined by which condition (intervention or control) was in place in the clinic waiting room during the patient's first visit within the study period. An intent-to-treat analysis was used to compare STD incidence between intervention and control patients. The primary endpoint was time to diagnosis of incident laboratory-confirmed infections (gonorrhea, chlamydia, trichomoniasis, syphilis, and HIV), as identified through review of medical records and county STD surveillance registries. During 14.8 mo (average) of follow-up, 2,042 patients (5.3%) were diagnosed with incident STD (4.9%, intervention condition; 5.7%, control condition). In survival analysis, patients assigned to the intervention condition had significantly fewer STDs compared with the control condition (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84 to 0.99). CONCLUSIONS: Showing a brief video in STD clinic waiting rooms reduced new infections nearly 10% overall in three clinics. This simple, low-intensity intervention may be appropriate for adoption by clinics that serve similar patient populations. TRIAL REGISTRATION: http://www.ClinicalTrials.gov (#NCT00137670).

Quality initiatives. Respiratory instructions for CT examinations of the lungs: a hands-on guide.

In computed tomographic (CT) examinations of the lung, accurate visualization of the natural contrast between the low attenuation of air and the relatively higher attenuation of vessels, airways, and interstitial structures requires cooperative and coordinated respiratory maneuvers by the patient. Inadequate respiratory maneuvers can influence differences in lung attenuation and lead to misinterpretation by (a) increasing attenuation to simulate disease in normal patients, (b) decreasing attenuation to simulate normal contrast in patients with disease, or (c) creating motion artifacts. For respiratory maneuvers to be effective, patients have to be instructed before the examination and coached during it. However, comprehensive descriptions of such instructions and coaching are lacking in the radiology literature. Therefore, respiratory instructions specifically for use in thoracic CT examinations have been devised. Along with patient coaching, use of these instructions can improve image quality. With this hands-on guide, both radiologists and technologists can optimize the respiratory instructions given to their patients and thereby improve the quality of thoracic CT examinations.

Aerosol furosemide for dyspnea: High-dose controlled delivery does not improve effectiveness.

Published studies have shown great variability in response when aerosolized furosemide has been tested as a palliative treatment for dyspnea. We hypothesized that a higher furosemide dose with controlled aerosol administration would produce consistent dyspnea relief. We optimized deposition by controlling inspiratory flow (300-500mL/s) and tidal volume (15% predicted vital capacity) while delivering 3.4µm aerosol from either saline or 80mg of furosemide. We induced dyspnea in healthy subjects by varying inspired PCO2 while restricting minute ventilation. Subjects rated "Breathing Discomfort" on a Visual Analog Scale (BDVAS, 100% Full Scale≡intolerable). At the PETCO2 producing 60% BDVAS pre-treatment, furosemide produced a clinically meaningful reduction of BDVAS (i.e., >20% FS) in 5/11 subjects; saline reduced dyspnea in 3/11 subjects; neither treatment worsened dyspnea in any subject. Furosemide and saline treatment effects were not statistically different. There were no significant adverse events. Higher furosemide dose and controlled delivery did not improve consistency of treatment effect compared with prior studies.

Aerosol furosemide for dyspnea: Controlled delivery does not improve effectiveness.

Aerosolized furosemide has been shown to relieve dyspnea; nevertheless, all published studies have shown great variability in response. This dyspnea relief is thought to result from the stimulation of slowly adapting pulmonary stretch receptors simulating larger tidal volume. We hypothesized that better control over aerosol administration would produce more consistent dyspnea relief; we used a clinical ventilator to control inspiratory flow and tidal volume. Twelve healthy volunteers inhaled furosemide (40mg) or placebo in a double blind, randomized, crossover study. Breathing Discomfort was induced by hypercapnia during constrained ventilation before and after treatment. Both treatments reduced breathing discomfort by 20% full scale. Effectiveness of aerosol furosemide treatment was weakly correlated with larger tidal volume. Response to inhaled furosemide was inversely correlated to furosemide blood level, suggesting that variation among subjects in the fate of deposited drug may determine effectiveness. We conclude that control of aerosol delivery conditions does not improve consistency of treatment effect; we cannot, however, rule out placebo effect.

Central airway mechanics and flow limitation in acquired tracheobronchomalacia.

BACKGROUND: Acquired tracheobronchomalacia (TBM) can cause central airway collapse in patients with COPD and may worsen airflow obstruction and symptoms. It is usually not known whether central airway malacia contributes to airflow obstruction. This study was undertaken to quantify central airway collapsibility and relate it to expiratory flow limitation in patients with TBM. METHODS: Eighty patients evaluated for acquired TBM and 4 healthy control subjects were studied with measurements of central airway narrowing derived from bronchoscopic videotapes and simultaneous pressure measurements in the trachea and esophagus. Tracheal narrowing was assessed by a shape index and plotted against the transtracheal pressure to measure collapsibility. Subsequently, airflow and transpulmonary pressure (PL) were measured to identify expiratory flow limitation during quiet breathing and to determine the critical PL required for maximum expiratory flow. RESULTS: Tracheal collapsibility varied widely among patients. Some had profound tracheal narrowing during quiet breathing, and others showed substantial collapse only during forced exhalation. Of the patients, 15% were not flow limited during quiet breathing, 53% were flow limited throughout exhalation, and 30% were flow limited only during the latter part of the exhalation. Patients with flow limitation at rest showed greater tracheal narrowing than those without (p = 0.009), but the severity of expiratory flow limitation was not closely related to tracheal collapsibility. Twenty-three patients were flow limited during quiet exhalation at PLs that did not cause central airway collapse. CONCLUSIONS: In TBM, central airway collapse is not closely related to airflow obstruction, and expiratory flow limitation at rest often occurs in peripheral airways without central airway collapse.

Cytokine release following recruitment maneuvers.

BACKGROUND: There are reports of rigors and/or clinical deterioration following recruitment maneuvers (RMs), leading us to question whether the use of sustained high-pressure inflation could lead to release of inflammatory mediators. METHODS: Prospective cohort study of 26 patients with ARDS receiving mechanical ventilation. A single RM was performed during which the mean airway pressure was increased to 40 cm H2O and held constant for a period of 30 s. The concentration of nine cytokines (interleukin [IL]-1, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-alpha, Fas ligand, vascular endothelial growth factor, TNF receptor 1, TNF receptor 2) was measured longitudinally at three time points: prior to initiation of the RM, 5 min after the RM, and 60 min after the RM. RESULTS: RMs were tolerated well from a hemodynamic perspective. Oxygenation improved as reflected by an increased Pao2/fraction of inspired oxygen (Fio2) ratio from 140+/-49 at baseline to 190+/-78 (mean+/-SD) at 5 min after the RM (p=0.01). At 60 min, the increase in Pao2/Fio2 ratio, to 172+/-76, was no longer significant (p=0.1). There were no important changes in the levels of any of the measured cytokines at 5 min or 60 min following RM as compared with the baseline levels. CONCLUSIONS: The results of our study demonstrate that recruitment maneuvers are well tolerated in patients with ARDS. Our data suggest no major hemodynamic or immunologic evidence of deterioration within the first hour of RM. In particular, cytokines, previously related to worsening lung injury and distal organ failure in patients with ARDS, are not elevated by use of an RM. Registered at: www.clinicaltrials.gov as NCT00127491.

Transpulmonary pressures and lung mechanics with glossopharyngeal insufflation and exsufflation beyond normal lung volumes in competitive breath-hold divers.

Throughout life, most mammals breathe between maximal and minimal lung volumes determined by respiratory mechanics and muscle strength. In contrast, competitive breath-hold divers exceed these limits when they employ glossopharyngeal insufflation (GI) before a dive to increase lung gas volume (providing additional oxygen and intrapulmonary gas to prevent dangerous chest compression at depths recently greater than 100 m) and glossopharyngeal exsufflation (GE) during descent to draw air from compressed lungs into the pharynx for middle ear pressure equalization. To explore the mechanical effects of these maneuvers on the respiratory system, we measured lung volumes by helium dilution with spirometry and computed tomography and estimated transpulmonary pressures using an esophageal balloon after GI and GE in four competitive breath-hold divers. Maximal lung volume was increased after GI by 0.13-2.84 liters, resulting in volumes 1.5-7.9 SD above predicted values. The amount of gas in the lungs after GI increased by 0.59-4.16 liters, largely due to elevated intrapulmonary pressures of 52-109 cmH(2)O. The transpulmonary pressures increased after GI to values ranging from 43 to 80 cmH(2)O, 1.6-2.9 times the expected values at total lung capacity. After GE, lung volumes were reduced by 0.09-0.44 liters, and the corresponding transpulmonary pressures decreased to -15 to -31 cmH(2)O, suggesting closure of intrapulmonary airways. We conclude that the lungs of some healthy individuals are able to withstand repeated inflation to transpulmonary pressures far greater than those to which they would normally be exposed.

Volume-related and volume-independent effects of posture on esophageal and transpulmonary pressures in healthy subjects.

Ventilator management decisions in acute lung injury could be better informed with knowledge of the patient's transpulmonary pressure, which can be estimated using measurements of esophageal pressure. Esophageal manometry is seldom used for this, however, in part because of a presumed postural artifact in the supine position. Here, we characterize the magnitude and variability of postural effects on esophageal pressure in healthy subjects to better assess its significance in patients with acute lung injury. We measured the posture-related changes in relaxation volume and total lung capacity in 10 healthy subjects in four postures: upright, supine, prone, and left lateral decubitus. Then, in the same subjects, we measured static pressure-volume characteristics of the lung over a wide range of lung volumes in each posture by using an esophageal balloon catheter. Transpulmonary pressure during relaxation (PLrel) averaged 3.7 (SD 2.0) cmH2O upright and -3.3 (SD 3.2) cmH2O supine. Approximately 58% of the decrease in PLrel between the upright and supine postures was due to a corresponding decrease in relaxation volume. The remaining 2.9-cmH2O difference is consistent with reported values of a presumed postural artifact. Relaxation volumes and pressures in prone and lateral postures were intermediate. To correct estimated transpulmonary pressure for the effect of lying supine, we suggest adding 3 cmH2O (95% confidence interval: -1 to +7 cmH2O). We conclude that postural differences in estimated transpulmonary pressure at a given lung volume are small compared with the substantial range of PLrel in patients with acute lung injury.