Air pollution, weather and positive airway pressure treatment adherence in adults with sleep apnea: a retrospective community-based repeated-measures longitudinal study.

We assessed the relation between air pollution, weather, and adherence to positive airway pressure (PAP) therapy in a retrospective community-based repeated-measures study of adults with obstructive sleep apnea who purchased PAP devices from a registered provider between 2013 and 2017 (Ottawa, Ontario, Canada) and had at least one day of data. Daily PAP-derived data, air pollution, and weather databases were linked using postal code. The exposures were mean nocturnal (8:00 p.m. to 8:00 a.m.) (i) residential concentrations of nitrogen dioxide (NO2 ), fine particulate matter <=2.5 µm (PM2.5 ), ozone (O3 ), and Air Quality Health Index (AQHI), and (ii) temperature, relative humidity, and barometric pressure. Covariates in the main model were demographics, season, exposure year, and PAP therapy mode. We analysed 8148 adults (median age of 54 years and 61% men) and 2,071,588 days of data. Based on daily data, the median (interquartile range) daily PAP usage was 416 (323-487) min. Using mixed-effect regression analyses to incorporate daily data and clustering by individuals, we found a statistically significant decrease in adherence for increased levels of NO2 , PM2.5 , and AQHI. The largest effect was for NO2 : a decrease in daily PAP use while comparing the highest versus lowest quartiles (Qs) was 3.4 (95% confidence interval [CI] 2.8-3.9) min. Decreased PAP adherence was also associated with increased temperature (Q4 versus Q1: 2.6 [95% CI: 1.5-3.7] min) and decreased barometric pressure (Q1 versus Q4: 2.0 [95% CI 1.5-2.5] min). We observed modest but statistically significant acute effects of air pollution and weather on daily PAP adherence.

Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement.

Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. Methods: An inter-professional, multidisciplinary, international committee with various stakeholders was formed. Three working groups (the historical policy origins, impact of current policy, and international PAP coverage models) met and performed literature reviews and discussions. Using surveys and an iterative discussion-based consensus process, the policy statement recommendations were created. Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities.

Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field.

Association of clinically significant obstructive sleep apnoea with risks of contracting COVID-19 and serious COVID-19 complications: a retrospective population-based study of health administrative data.

RATIONALE/OBJECTIVES: Despite plausible pathophysiological mechanisms, more research is needed to confirm the relationship between obstructive sleep apnoea (OSA) and the risk of COVID-19 infection or COVID-19-related serious complications. METHODS: We conducted a retrospective population-based cohort study using provincial health administrative data (Ontario, Canada). Adults with physician-diagnosed OSA who received positive airway pressure therapy in the 5 years prepandemic (OSA group) were propensity score matched by baseline characteristics to individuals in the general population at low risk of OSA (non-OSA group) using inverse probability of treatment weighting. Weighted HRs of (1) a positive COVID-19 test and (2) COVID-19-related emergency department (ED) visits, hospitalisations, intensive care unit (ICU) admissions and mortality, within 12 months of pandemic onset, were compared between groups. We also evaluated the impact of comorbid cardiometabolic or chronic airways disease. RESULTS: We identified and matched 324 029 individuals in the OSA group to 4 588 200 individuals in the non-OSA group. Compared with the non-OSA group, those in the OSA group were at a greater hazard of testing positive for COVID-19 (HR=1.17, 95% CI 1.13 to 1.21), having a COVID-19-related ED visit (HR=1.62, 95% CI 1.51 to 1.73), hospitalisation (HR=1.50, 95% CI 1.37 to 1.65) or ICU admission (HR=1.53, 95% CI 1.27 to 1.84). COVID-19-related 30-day mortality was not different (HR=0.98, 95% CI 0.82 to 1.16).We found that for the OSA group, comorbid airways disease but not cardiometabolic conditions increased the hazards of COVID-19-related outcomes, including mortality. CONCLUSION: In this large population-based study, we demonstrated that a recent diagnosis of OSA requiring treatment was associated with an increased hazard of testing positive for COVID-19 and serious COVID-19-related complications, particularly in those with co-existing chronic airways disease.

The rs579459 ABO gene polymorphism and risk of incident cardiovascular events in obstructive sleep apnea: a pilot study.

PURPOSE: We have previously shown that the TT genotype (rs579459 location of the ABO gene) is significantly associated with circulating levels of e-selectin in patients with suspected obstructive sleep apnea (OSA). We hypothesized that this genotype would be associated with incident cardiovascular disease (CVD). METHODS: Patients with suspected OSA who had a full diagnostic polysomnogram from 2003 to 2011 were recruited; CV events occurring within 8 years of polysomnography were identified by linkage to provincial health databases. Cox proportional hazards models were used to evaluate the incidence of first CV events as a function of the rs579459 genotype. RESULTS: In this targeted study, 408 patients were studied, and 39 incident events were identified. A larger proportion of patients with the TT genotype had an event (31/247; 12.6%) than the CT and CC genotypes (8/161; 5.0%); in univariate analysis, the TT genotype was significantly associated with CV events (HR = 2.53; 95% CI = 1.16-5.51, p = 0.02). After adjustment for age, AHI, sex, smoking, diabetes, statin use, and BMI, the TT genotype remained a significant predictor (HR = 2.35; 95% CI = 1.02-5.42, p = 0.046). No events were found in patients with an absence of both OSA and the TT genotype (N = 30). The effect of the SNP was partially (16.2%) mediated by e-selectin levels. CONCLUSION: This is the first study to examine genetic variants as a risk factor for incident CVD in the context of OSA. Although these results are preliminary and in need of replication, it suggests that genetic markers may become useful in helping to guide precision clinical care.

Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men.

KEY POINTS: Intermittent hypoxia leads to long-lasting increases in muscle sympathetic nerve activity and blood pressure, contributing to increased risk for hypertension in obstructive sleep apnoea patients. We determined whether augmented vascular responses to increasing sympathetic vasomotor outflow, termed sympathetic neurovascular transduction (sNVT), accompanied changes in blood pressure following acute intermittent hypercapnic hypoxia in men. Lower body negative pressure was utilized to induce a range of sympathetic vasoconstrictor firing while measuring beat-by-beat blood pressure and forearm vascular conductance. IH reduced vascular shear stress and steepened the relationship between diastolic blood pressure and sympathetic discharge frequency, suggesting greater systemic sNVT. Our results indicate that recurring cycles of acute intermittent hypercapnic hypoxia characteristic of obstructive sleep apnoea could promote hypertension by increasing sNVT. ABSTRACT: Acute intermittent hypercapnic hypoxia (IH) induces long-lasting elevations in sympathetic vasomotor outflow and blood pressure in healthy humans. It is unknown whether IH alters sympathetic neurovascular transduction (sNVT), measured as the relationship between sympathetic vasomotor outflow and either forearm vascular conductance (FVC; regional sNVT) or diastolic blood pressure (systemic sNVT). We tested the hypothesis that IH augments sNVT by exposing healthy males to 40 consecutive 1 min breathing cycles, each comprising 40 s of hypercapnic hypoxia ( PETCO2 : +4 ± 3 mmHg above baseline; PETO2 : 48 ± 3 mmHg) and 20 s of normoxia (n = 9), or a 40 min air-breathing control (n = 7). Before and after the intervention, lower body negative pressure (LBNP; 3 min at -15, -30 and -45 mmHg) was applied to elicit reflex increases in muscle sympathetic nerve activity (MSNA, fibular microneurography) when clamping end-tidal gases at baseline levels. Ventilation, arterial pressure [systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP)], brachial artery blood flow ( Q̇BA ), FVC ( Q̇BA /MAP) and MSNA burst frequency were measured continuously. Following IH, but not control, ventilation [5 L min-1 ; 95% confidence interval (CI) = 1-9] and MAP (5 mmHg; 95% CI = 1-9) were increased, whereas FVC (-0.2 mL min-1  mmHg-1 ; 95% CI = -0.0 to -0.4) and mean shear rate (-21.9 s-1 ; 95% CI = -5.8 to -38.0; all P < 0.05) were reduced. Systemic sNVT was increased following IH (0.25 mmHg burst-1  min-1 ; 95% CI = 0.01-0.49; P < 0.05), whereas changes in regional forearm sNVT were similar between IH and sham. Reductions in vessel wall shear stress and, consequently, nitric oxide production may contribute to heightened systemic sNVT and provide a potential neurovascular mechanism for elevated blood pressure in obstructive sleep apnoea.

Outcomes of Critically Ill Patients Who Have Serotype 5 Invasive Pneumococcal Disease.

PURPOSE: To determine whether invasive pneumococcal disease (IPD) due to serotype 5, which occurred as a local outbreak in 2006 to 2007, is associated with intensive care unit (ICU) admission, hospital mortality, or organ supports in those who are critically ill. MATERIALS AND METHODS: Retrospective review of patients who presented with IPD to 2 tertiary hospitals in Vancouver, Canada, from July 2004 to June 2007. We compared patient characteristics, interventions, and outcomes between patients who had serotype 5 and other serotypes using bivariate and multivariate analyses. RESULTS: A total of 149 patients had serotype 5 and 106 had nonserotype 5. Patients with serotype 5 were younger, had lower prevalence of comorbid diseases, and had higher rates of substance use than patients with nonserotype 5. There were no differences in chest tube placement for complications of pneumonia or in ICU admission. Frequency of necrotizing pneumonia and hospital mortality were lower in the serotype 5 group. For the 71 patients with IPD who were admitted to ICU, there was no difference in severity of illness, ICU length of stay, or ICU mortality between the groups. There was also no difference in organ supports except that the serotype 5 group was more likely to receive vasopressors. CONCLUSION: Serotype 5 in patients who have IPD is associated with no difference in ICU admission but with increased use of vasopressors and lower hospital mortality.

Obstructive Sleep Apnea Severity and the Risk of Occupational Injury: A Prospective Observational Cohort.

OBJECTIVE: To determine whether patients with obstructive sleep apnea (OSA) are at increased risk of occupational injury (OI) METHODS: Working patients (aged 18 to 65 who reported more than 10 h of work per week) who were referred to the University of British Columbia Sleep Laboratory for suspected OSA for polysomnogram (PSG) were recruited from 2003 to 2011. Patients completed an extensive survey the night of their PSG. Validated OI was obtained by linking patient data to Workers Compensation Board Claims Data. RESULTS: 1109 workers were studied; mean age was 47.1 years, median AHI was 15.0/h, median BMI was 30 kg/m2, 70.2% were male and 29% of patients worked in physical or manual related occupations. 78 patients (7.03%) suffered 140 OI in the 5 years after PSG. In a multivariate logistic regression model, OSA severity [defined as a log(AHI + 1)] was a significant predictor of OI (p = 0.04) after controlling for age, sex, BMI, and physical or manual related occupations. Patients with moderate and severe OSA had approximately two times the odds of an OI compared to patients without OSA (OR 1.99, 95% CI 0.96-4.44 and 2.00, 95% CI 0.96-4.49 for moderate and severe OSA groups, respectively). CONCLUSIONS: In this prospective study, OSA severity was independently associated with an increased risk of OI.

Obstructive Sleep Apnea Severity, Body Mass Index, and Circulating Levels of Cellular Adhesion Molecules.

PURPOSE: To investigate the relationship between obstructive sleep apnea (OSA) severity, body mass index (BMI), and circulating levels of inflammatory adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin). METHODS: A cross-sectional clinical cohort study on all consecutive adults referred to the University of British Columbia (UBC) Sleep Laboratory for a polysomnogram (PSG) for suspected OSA provided a morning blood sample. Samples were analyzed with multiplex immune assay (MilliporeSigma, CA) to assess the levels of adhesion molecules. RESULTS: 488 patients were studied; the majority were male (68%) with a mean age of 50 yrs, mean AHI of 23 events/hour, and mean BMI of 32 kg/m2. In multivariable linear regression models, all three adhesion molecules were significantly associated with BMI (E-selectin p < 0.0001; ICAM-1 p = 0.0007; VCAM-1 p = 0.0003). However, only E-selectin was independently associated with AHI (p = 0.02); there was no significant interaction between AHI and BMI for E-selectin (p = 0.33). CONCLUSIONS: Although all three adhesion molecules were associated with BMI, only E-selectin was independently associated with OSA severity. Future studies are needed to determine the clinical significance of the relationship between E-selectin and OSA.

Continuous Positive Airway Pressure Use for Obstructive Sleep Apnea in Acute, Traumatic Tetraplegia.

OBJECTIVE: To describe continuous positive airway pressure (CPAP) use for treatment of obstructive sleep apnea (OSA) in acute tetraplegia, including adherence rates and associated factors. DESIGN: Secondary analysis of CPAP data from a multinational randomized controlled trial. SETTING: Inpatient rehabilitation units of 11 spinal cord injury centers. PARTICIPANTS: People with acute, traumatic tetraplegia and OSA (N=79). INTERVENTIONS: Autotitrating CPAP for OSA for 3 months. MAIN OUTCOME MEASURES: Adherence measured as mean daily hours of use. Adherent (yes/no) was defined as an average of at least 4 hours a night throughout the study. Regression analyses determined associations between baseline factors and adherence. CPAP device pressure and leak data were analyzed descriptively. RESULTS: A total of 79 participants from 10 spinal units (91% men; mean age ± SD, 46±16; 78±64d postinjury) completed the study in the treatment arm and 33% were adherent. Mean daily CPAP use ± SD was 2.9±2.3 hours. Better adherence was associated with more severe OSA (P=.04) and greater CPAP use in the first week (P<.01). Average 95th percentile pressure was low (9.3±1.7 cmH2O) and 95th percentile leak was high (27.1±13.4 L/min). CONCLUSION: Adherence to CPAP after acute, traumatic tetraplegia is low. Early acceptance of therapy and more severe OSA predict CPAP use over 3 months. People with acute tetraplegia require less pressure to treat their OSA than the nondisabled; however, air leak is high. These findings highlight the need for further investigation of OSA treatment in acute tetraplegia.

Diagnostic accuracy of a two-stage model for detecting obstructive sleep apnoea in chronic tetraplegia.

BACKGROUND: Obstructive sleep apnoea (OSA) is highly prevalent in people with spinal cord injury (SCI). Polysomnography (PSG) is the gold-standard diagnostic test for OSA, however PSG is expensive and frequently inaccessible, especially in SCI. A two-stage model, incorporating a questionnaire followed by oximetry, has been found to accurately detect moderate to severe OSA (MS-OSA) in a non-disabled primary care population. This study investigated the accuracy of the two-stage model in chronic tetraplegia using both the original model and a modified version for tetraplegia. METHODS: An existing data set of 78 people with tetraplegia was used to modify the original two-stage model. Multivariable analysis identified significant risk factors for inclusion in a new tetraplegia-specific questionnaire. Receiver operating characteristic (ROC) curve analyses of the questionnaires and oximetry established thresholds for diagnosing MS-OSA. The accuracy of both models in diagnosing MS-OSA was prospectively evaluated in 100 participants with chronic tetraplegia across four international SCI units. RESULTS: Injury completeness, sleepiness, self-reported snoring and apnoeas were included in the modified questionnaire, which was highly predictive of MS-OSA (ROC area under the curve 0.87 (95% CI 0.79 to 0.95)). The 3% oxygen desaturation index was also highly predictive (0.93 (0.87-0.98)). The two-stage model with modified questionnaire had a sensitivity and specificity of 83% (66-93) and 88% (75-94) in the development group, and 77% (65-87) and 81% (68-90) in the validation group. Similar results were demonstrated with the original model. CONCLUSION: Implementation of this simple alternative to full PSG could substantially increase the detection of OSA in patients with tetraplegia and improve access to treatments. TRIAL REGISTRATION NUMBER: Results, ACTRN12615000896572 (The Australian and New Zealand Clinical Trials Registry) and pre-results, NCT02176928 (clinicaltrials.gov).

Obstructive sleep apnoea and frequency of occupational injury.

We sought to determine whether patients with obstructive sleep apnoea (OSA) are at increased risk of occupational injury (OI). Patients referred to the University of British Columbia Hospital Sleep Laboratory for suspected OSA (May 2003 to July 2011 were recruited and rates and types of validated OI (that caused at least 1 day of disability) in the 5 years prior to polysomnography were calculated. In a sample of 1236, patients with OSA were twice as likely (OR=1.93, 95% CI 1.06 to 3.50, p=0.03) to suffer at least one OI compared with patients without OSA. This association was attenuated (OR=1.76, CI 0.86 to 3.59, p=0.12) after controlling for confounders. In a secondary analysis, patients with OSA were almost three times more likely (OR=2.88, CI 1.02 to 8.08, p=0.05) to suffer from an injury more likely related to reduced vigilance (eg, a fall or commercial motor vehicle crash) when compared with patients without OSA, and this again was attenuated after controlling for confounders (OR=2.42, CI 0.085 to 6.93, p=0.10).

Cardiovascular consequences of obstructive sleep apnea.

PURPOSE OF REVIEW: There is an increased awareness of obstructive sleep apnea (OSA) and its potential impact on cardiovascular diseases (CVDs). The number of patients diagnosed with OSA is likely to increase as the obesity epidemic continues to grow. We review recent publications that have examined the links between OSA and CVD. RECENT FINDINGS: The cardiovascular consequences of OSA include hypertension, strokes, atrial fibrillation, and heart failure. It is likely that these are related to OSA-induced changes in endothelial dysfunction, oxidative stress, and systemic inflammation. The mainstay of treatment of OSA remains positive airway pressure devices (PAP), but issues of adherence continue to plague effective management. Oral appliances may also be a suitable alternative and may have a similar effect on blood pressure as PAP. To date, randomized trials have verified a significant (though relatively modest) impact of PAP on blood pressure, and some have shown an improvement in glucose control in diabetic individuals. However, it is unclear whether PAP prevents cardiovascular events in patients with OSA, although patients well managed and adherent with PAP seem to do better than those who are nonadherent. SUMMARY: The mortality and morbidity associated with OSA are reduced in patients well managed with PAP. However, we await the results of large randomized clinical trials to definitely determine whether PAP reduces the rate of cardiovascular events. Current efforts aimed at identifying biomarkers in OSA may offer a strategy for personalized treatment plans of OSA patients.

An Official American Thoracic Society Statement: The Importance of Healthy Sleep. Recommendations and Future Priorities.

RATIONALE: Despite substantial public interest, few recommendations on the promotion of good sleep health exist to educate health care providers and the general public on the importance of sleep for overall health. OBJECTIVES: The aim of this American Thoracic Society (ATS) statement is to provide a review of the current scientific literature to assist health care providers, especially pulmonologists and sleep physicians, in making recommendations to patients and the general public about the importance of achieving good quality and adequate quantity of sleep. METHODS: ATS members were invited, based on their expertise in sleep medicine, and their conclusions were based on both empirical evidence identified after comprehensive literature review and clinical experience. MAIN RESULTS: We focus on sleep health in both children and adults, including the impact of occupation on sleep, the public health implications of drowsy driving, and the common sleep disorders of obstructive sleep apnea and insomnia. This ATS statement also delineates gaps in research and knowledge that should be addressed and lead to new focused research priorities to advance knowledge in sleep and sleep health. CONCLUSIONS: Good quality and quantity of sleep are essential for good health and overall quality of life; therefore a strong recommendation was made for the implementation of public education programs on the importance of sleep health.

Sleep Stage Coordination of Respiration and Swallowing: A Preliminary Study.

Swallowing is an important physiological response that protects the airway. Although aspiration during sleep may cause aspiration pneumonia, the mechanisms responsible have not yet been elucidated. We evaluated the coordination between respiration and swallowing by infusing water into the pharynx of healthy young adults during each sleep stage. Seven normal subjects participated in the study. During polysomnography recordings, to elicit a swallow we injected distilled water into the pharynx during the awake state and each sleep stage through a nasal catheter. We assessed swallow latency, swallow apnea time, the respiratory phase during a swallow, the number of swallows, and coughing. A total number of 79 swallows were recorded. The median swallow latency was significantly higher in stage 2 (10.05 s) and stage 3 (44.17 s) when compared to awake state (4.99 s). The swallow latency in stage 3 showed a very wide interquartile range. In two subjects, the result was predominantly prolonged compared to the other subjects. There was no significant difference in the swallow apnea time between sleep stages. The presence of inspiration after swallowing, repetitive swallowing, and coughing after swallowing was more frequent during sleep than when awake. This study suggests that the coordination between respiration and swallowing as a defense mechanism against aspiration was impaired during sleep. Our results supported physiologically the fact that healthy adult individuals aspirate pharyngeal secretions during sleep.

Will This Hemodynamically Unstable Patient Respond to a Bolus of Intravenous Fluids?

IMPORTANCE: Fluid overload occurring as a consequence of overly aggressive fluid resuscitation may adversely affect outcome in hemodynamically unstable critically ill patients. Therefore, following the initial fluid resuscitation, it is important to identify which patients will benefit from further fluid administration. OBJECTIVE: To identify predictors of fluid responsiveness in hemodynamically unstable patients with signs of inadequate organ perfusion. DATA SOURCES AND STUDY SELECTION: Search of MEDLINE and EMBASE (1966 to June 2016) and reference lists from retrieved articles, previous reviews, and physical examination textbooks for studies that evaluated the diagnostic accuracy of tests to predict fluid responsiveness in hemodynamically unstable adult patients who were defined as having refractory hypotension, signs of organ hypoperfusion, or both. Fluid responsiveness was defined as an increase in cardiac output following intravenous fluid administration. DATA EXTRACTION: Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. A bivariate mixed-effects binary regression model was used to pool the sensitivities, specificities, and LRs across studies. RESULTS: A total of 50 studies (N = 2260 patients) were analyzed. In all studies, indices were measured before assessment of fluid responsiveness. The mean prevalence of fluid responsiveness was 50% (95% CI, 42%-56%). Findings on physical examination were not predictive of fluid responsiveness with LRs and 95% CIs for each finding crossing 1.0. A low central venous pressure (CVP) (mean threshold <8 mm Hg) was associated with fluid responsiveness (positive LR, 2.6 [95% CI, 1.4-4.6]; pooled specificity, 76%), but a CVP greater than the threshold made fluid responsiveness less likely (negative LR, 0.50 [95% CI, 0.39-0.65]; pooled sensitivity, 62%). Respiratory variation in vena cava diameter measured by ultrasound (distensibility index >15%) predicted fluid responsiveness in a subgroup of patients without spontaneous respiratory efforts (positive LR, 5.3 [95% CI, 1.1-27]; pooled specificity, 85%). Patients with less vena cava distensibility were not as likely to be fluid responsive (negative LR, 0.27 [95% CI, 0.08-0.87]; pooled sensitivity, 77%). Augmentation of cardiac output or related parameters following passive leg raising predicted fluid responsiveness (positive LR, 11 [95% CI, 7.6-17]; pooled specificity, 92%). Conversely, the lack of an increase in cardiac output with passive leg raising identified patients unlikely to be fluid responsive (negative LR, 0.13 [95% CI, 0.07-0.22]; pooled sensitivity, 88%). CONCLUSIONS AND RELEVANCE: Passive leg raising followed by measurement of cardiac output or related parameters may be the most useful test for predicting fluid responsiveness in hemodynamically unstable adults. The usefulness of respiratory variation in the vena cava requires confirmatory studies.

Gas density alters expiratory time constants before and after experimental lung injury.

NEW FINDINGS: What is the central question of this study? Does the induction of a model of lung injury affect the expiratory time constant (τE) in terms of either total duration or morphology? Does ventilation with gases of different densities alter the duration or morphology of τE either before or after injury? What is the main finding and its importance? The use of sulfur hexafluoride in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both nitrogen and helium mixtures. Sulfur hexafluoride mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with nitrogen and helium mixtures. Acute lung injury is characterized by regional heterogeneity of lung resistance and elastance that may lead to regional heterogeneity of expiratory time constants (τE). We hypothesized that increasing airflow resistance by using inhaled sulfur hexafluoride (SF6) would lengthen time constants and decrease their heterogeneity in an experimental model of lung injury when compared with nitrogen or helium mixtures. To overcome the limitations of a single-compartment model, we employed a multisegment model of expiratory gas flow. An experimental model of lung injury was created using intratracheal injection of sodium polyacrylate in anaesthetized and mechanically ventilated female Yorkshire-cross pigs (n = 7). The animals were ventilated with 50% O2 and the remaining 50% as nitrogen (N2), helium (He) or sulfur hexafluoride (SF6). Values for τE decreased with injury and were more variable after injury than before (P < 0.001). Values for τE increased throughout expiration both before and after injury, and the rate of increase in τE was lessened by SF6 (P < 0.001 when compared with N2 both before and after injury). Altering the inhaled gas density did not affect indices of oxygenation, dead space or shunt. The use of SF6 in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both N2 and He mixtures. Importantly, SF6 mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with N2 and He mixtures.