Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis.

Thrombotic complications occur at high rates in hospitalized patients with COVID-19, yet the impact of intensive antithrombotic therapy on mortality is uncertain. We examined in-hospital mortality with intermediate- compared to prophylactic-dose anticoagulation, and separately with in-hospital aspirin compared to no antiplatelet therapy, in a large, retrospective study of 2785 hospitalized adult COVID-19 patients. In this analysis, we established two separate, nested cohorts of patients (a) who received intermediate- or prophylactic-dose anticoagulation ("anticoagulation cohort", N = 1624), or (b) who were not on home antiplatelet therapy and received either in-hospital aspirin or no antiplatelet therapy ("aspirin cohort", N = 1956). To minimize bias and adjust for confounding factors, we incorporated propensity score matching and multivariable regression utilizing various markers of illness severity and other patient-specific covariates, yielding treatment groups with well-balanced covariates in each cohort. The primary outcome was cumulative incidence of in-hospital death. Among propensity score-matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate- compared to prophylactic-dose anticoagulation was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.518 [0.308-0.872]). Among propensity-score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in-hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.522 [0.336-0.812]). In this propensity score-matched, observational study of COVID-19, intermediate-dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in-hospital death.

Abnormalities of Aspiration and Swallowing Function in Survivors of Acute Respiratory Failure.

The mechanisms responsible for aspiration are relatively unknown in patients recovering from acute respiratory failure (ARF) who required mechanical ventilation. Though many conditions may contribute to swallowing dysfunction, alterations in laryngeal structure and swallowing function likely play a role in the development of aspiration. At four university-based tertiary medical centers, we conducted a prospective cohort study of ARF patients who required intensive care and mechanical ventilation for at least 48 h. Within 72 h after extubation, a Fiberoptic Flexible Endoscopic Evaluation of Swallowing (FEES) examination was performed. Univariate and multivariable analyses examined the relationship between laryngeal structure and swallowing function abnormalities. Aspiration was the primary outcome, defined as a Penetration- Aspiration Scale (PAS) score of 6 or greater. Two other salient signs of dysphagia-spillage and residue-were secondary outcomes. A total of 213 patients were included in the final analysis. Aspiration was detected in 70 patients (33%) on at least one bolus. The most commonly aspirated consistency was thin liquids (27%). In univariate analyses, several abnormalities in laryngeal anatomy and structural movement were significantly associated with aspiration, spillage, and residue. In a multivariable analysis, the only variables that remained significant with aspiration were pharyngeal weakness (Odds ratio = 2.57, 95%CI = 1.16-5.84, p = 0.019) and upper airway edema (Odds ratio = 3.24, 95%CI = 1.44-7.66, p = 0.004). These results demonstrated that dysphagia in ARF survivors is multifactorial and characterized by both anatomic and physiologic abnormalities. These findings may have important implications for the development of novel interventions to treat dysphagia in ARF survivors.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT02363686, Aspiration in Acute Respiratory Failure Survivors.

The Association Between Endotracheal Tube Size and Aspiration (During Flexible Endoscopic Evaluation of Swallowing) in Acute Respiratory Failure Survivors.

OBJECTIVES: To determine whether a modifiable risk factor, endotracheal tube size, is associated with the diagnosis of postextubation aspiration in survivors of acute respiratory failure. DESIGN: Prospective cohort study. SETTING: ICUs at four academic tertiary care medical centers. PATIENTS: Two hundred ten patients who were at least 18 years old, admitted to an ICU, and mechanically ventilated with an endotracheal tube for longer than 48 hours were enrolled. INTERVENTIONS: Within 72 hours of extubation, all patients received a flexible endoscopic evaluation of swallowing examination that entailed administration of ice, thin liquid, thick liquid, puree, and cracker boluses. Patient demographics, treatment variables, and hospital outcomes were abstracted from the patient's medical records. Endotracheal tube size was independently selected by the patient's treating physicians. MEASUREMENTS AND MAIN RESULTS: For each flexible endoscopic evaluation of swallowing examination, laryngeal pathology was evaluated, and for each bolus, a Penetration Aspiration Scale score was assigned. Aspiration (Penetration Aspiration Scale score ≥ 6) was further categorized into nonsilent aspiration (Penetration Aspiration Scale score = 6 or 7) and silent aspiration (Penetration Aspiration Scale score = 8). One third of patients (n = 68) aspirated (Penetration Aspiration Scale score ≥ 6) on at least one bolus, 13.6% (n = 29) exhibited silent aspiration, and 23.8% (n = 50) exhibited nonsilent aspiration. In a multivariable analysis, endotracheal tube size (≤ 7.5 vs ≥ 8.0) was significantly associated with patients exhibiting any aspiration (Penetration Aspiration Scale score ≥ 6) (p = 0.016; odds ratio = 2.17; 95% CI 1.14-4.13) and with risk of developing laryngeal granulation tissue (p = 0.02). CONCLUSIONS: Larger endotracheal tube size was associated with increased risk of aspiration and laryngeal granulation tissue. Using smaller endotracheal tubes may reduce the risk of postextubation aspiration.

Relationship Between Laryngeal Sensation, Length of Intubation, and Aspiration in Patients with Acute Respiratory Failure.

Dysphagia is common in hospitalized patients post-extubation and associated with poor outcomes. Laryngeal sensation is critical for airway protection and safe swallowing. However, current understanding of the relationship between laryngeal sensation and aspiration in post-extubation populations is limited. Acute respiratory failure patients requiring intensive care unit admission and mechanical ventilation received a Flexible Endoscopic Evaluation of Swallowing (FEES) within 72 h of extubation. Univariate and multivariable analyses were performed to examine the relationship between laryngeal sensation, length of intubation, and aspiration. Secondary outcomes included pharyngolaryngeal secretions, pneumonia, and diet recommendations. One-hundred and three patients met inclusion criteria. Fifty-one patients demonstrated an absent laryngeal adductor reflex (LAR). Altered laryngeal sensation correlated with the presence of secretions (p = 0.004). There was a significant interaction between the LAR, aspiration, and duration of mechanical ventilation. Altered laryngeal sensation was significantly associated with aspiration on FEES only in patients with a shorter length of intubation (p = 0.008). Patients with altered laryngeal sensation were prescribed significantly more restricted liquid (p = 0.03) and solid (p = 0.001) diets. No relationship was found between laryngeal sensation and pneumonia. There is a high prevalence of laryngeal sensory deficits in mechanically ventilated patients post-extubation. Altered laryngeal sensation was associated with secretions, aspiration, and modified diet recommendations especially in those patients with a shorter length of mechanical ventilation. These results demonstrate that laryngeal sensory abnormalities impact the development of post-extubation dysphagia.

"Deterioration to Door Time": An Exploratory Analysis of Delays in Escalation of Care for Hospitalized Patients.

BACKGROUND: Timely escalation of care for patients experiencing clinical deterioration in the inpatient setting is challenging. Deterioration on a general floor has been associated with an increased risk of death, and the early period of deterioration may represent a time during which admission to the intensive care unit (ICU) improves survival. Previous studies examining the association between delay from onset of clinical deterioration to ICU transfer and mortality are few in number and were conducted more than 10 years ago. OBJECTIVE: We aimed to evaluate the impact of delays in the escalation of care among clinically deteriorating patients in the current era of inpatient medicine. DESIGN AND PARTICIPANTS: This was a retrospective cohort study that analyzed data from 793 patients transferred from non-intensive care unit (ICU) inpatient floors to the medical intensive care unit (MICU), from 2011 to 2013 at an urban, tertiary, academic medical center. MAIN MEASURES: "Deterioration to door time (DTDT)" was defined as the time between onset of clinical deterioration (as evidenced by the presence of one or more vital sign indicators including respiratory rate, systolic blood pressure, and heart rate) and arrival in the MICU. KEY RESULTS: In our sample, 64.6 % had delays in care escalation, defined as greater than 4 h based on previous studies. Mortality was significantly increased beginning at a DTDT of 12.1 h after adjusting for age, gender, and severity of illness. CONCLUSIONS: Delays in the escalation of care for clinically deteriorating hospitalized patients remain frequent in the current era of inpatient medicine, and are associated with increased in-hospital mortality. Development of performance measures for the care of clinically deteriorating inpatients remains essential, and timeliness of care escalation deserves further consideration.

Oral Alimentation in Neonatal and Adult Populations Requiring High-Flow Oxygen via Nasal Cannula.

Use of high-flow oxygen via nasal cannula (HFO2-NC) is increasingly common in intensive care unit (ICU) settings. Despite the critical interface between respiration and swallowing, and the high acuity of patients in ICUs, the impact of HFO2-NC on feeding and swallowing is unknown. The present prospective, single-center, cohort study investigated the impact of HFO2-NC use on oral alimentation in neonatal and adult ICU patients. Oral alimentation status was evaluated in 100 consecutive ICU inpatients (50 neonatal and 50 adult) requiring HFO2-NC. Participant characteristics, respiratory support, successful initiation of oral feeding in neonates, and successful resumption of oral feeding in adults were recorded. Seventeen of 50 (34 %) neonates requiring HFO2-NC were deemed developmentally and medically appropriate by the neonatologist and nursing to begin oral alimentation. All 17 (100 %) were successful with initiation of oral feedings. Thirty-three of 50 (66 %) continued nil per os due to prematurity or medical conditions precluding oral alimentation at time of data collection. Thirty-nine of 50 (78 %) adults requiring HFO2-NC were deemed medically appropriate by the intensivist and nursing to resume oral alimentation (n = 34) or with a functional swallow without aspiration on FEES (n = 5). All 39 (100 %) resumed oral alimentation successfully. Eleven of 50 (22 %) continued nil per os due to severe respiratory issues precluding both swallow testing and oral alimentation at time of data collection. All developmentally and medically appropriate neonatal and adult patients requiring HFO2-NC were successful with either the introduction or resumption of oral alimentation. Patients requiring HFO2-NC who are identified as having feeding or swallowing issues should be referred for swallowing evaluations using the same criteria as patients who do not require HFO2-NC, as it is not the use of HFO2-NC but rather patient-specific determinants of feeding and swallowing readiness and their underlying medical conditions that impact readiness for oral alimentation status.

Protocol-Based Care versus Individualized Management of Patients in the Intensive Care Unit.

The delivery of evidence-based care in the high-acuity environment of the intensive care unit can be challenging. In an effort to help turn guidelines and standards of care into consistent and uniform practice, physicians and hospitals turn toward protocol-based medical care. A protocol can help guide a practitioner to make correct interventions, at the right time, and in the proper order when managing a given disease. But to be considered a success, a protocol must meet several standards. A protocol must facilitate consistent practice, guiding the practitioner to deliver care more consistently than without the protocol. A good protocol must also be in alignment with the provider's general practice and beliefs to assure wide adoption and complete penetrance. Finally, the protocol must deliver the most medically correct care-neither simplifying nor overcomplicating health care delivery. In addition to the care the protocol delivers, it must overcome other barriers to gain acceptance. These include concerns about protocol usage among medical trainees, physician concern regarding loss of autonomy, and the ceiling effect protocol-driven care places on expert practitioners, among other concerns. The aim of this article is to critically appraise what it means for a protocol to be considered successful with an aim toward improving protocol design and implementation in the future.

Tele-Critical Care Support Outside the Intensive Care Unit.

Tele-intensive care unit (ICU), or Tele Critical Care (TCC), has been in active use for 25 years and has expanded beyond the original model to support critically ill patients beyond the confines of the ICU. Here, the author reviews the role of TCC in supporting rapid response events, critical care in emergency departments, and disaster and pandemic responses. The ability to rapidly expand critical care services has important capacity and care quality implications. Moreover, as TCC infrastructure becomes less expensive, the opportunities to leverage this care modality also have potentially important financial benefits.

A tale of two ligands: angiopoietins, the endothelium, and outcomes.

Angiopoietins signal via the Tie-2 receptor and are essential molecules for vasculogenesis during development and in the adult state play roles in vascular stability as well as inflammation and appear to be involved in the dysregulation of the endothelium in illness. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are, respectively, agonists and competitive partial agonists, which have been found to undergo alterations in individuals with sepsis. In sepsis, Ang-2 levels are elevated and Ang-1 is decreased. In the previous issue of Critical Care, Fiusa and colleagues measure circulating Ang-1 and Ang-2 along with other growth factors in humans with febrile neutropenia. The authors found that an increased Ang-2/Ang-1 ratio, or an elevated Ang-2 level, at the time of an initial fever, is associated with subsequent development of septic shock and death. These findings validate that the Ang-2/Ang-1 balance, which is thought to reflect overall signaling via the Tie-2 receptor, is relevant to outcomes in patients with sepsis. Importantly, the specimens were obtained far in advance of the development of septic shock, suggesting that detectable alterations in this pathway may provide early clues regarding outcomes. This study adds to the evidence that angiopoietins are early markers of endothelial dysfunction in sepsis and provide prognostic information regarding outcomes.

Lung-Protective Ventilation Over 6 Years at a Large Academic Medical Center: An Evaluation of Trends, Adherence, and Perceptions of Benefit.

The main objective of this study was to evaluate trends in set tidal volumes across all adult ICUs at a large academic medical center over 6 years, with a focus on adherence to lung-protective ventilation (≤ 8-cc/kg ideal body weight). A secondary objective was to survey providers on their perceptions of lung-protective ventilation and barriers to its implementation. DESIGN: Retrospective observational analysis (primary objective) and cross-sectional survey study (secondary objective), both at a single center. PARTICIPANTS: Mechanically ventilated adult patients with a set tidal volume (primary objective) and providers rotating through the Medical and Neurosciences ICUs (secondary objective). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 2013 to 2018, the average initial set tidal volume (cc/kg ideal body weight) decreased from 8.99 ± 2.19 to 7.45±1.34 (p < 0.001). The cardiothoracic ICU had the largest change in tidal volume from 11.09 ± 1.96 in 2013 to 7.97 ± 1.03 in 2018 (p < 0.001). Although the majority of tidal volumes across all ICUs were between 6.58 and 8.01 (interquartile range) in 2018, 27% of patients were still being ventilated at volumes greater than 8-cc/kg ideal body weight. Most surveyed respondents felt there was benefit to lung-protective ventilation, though many did not routinely calculate the set tidal volume in cc/kg ideal body weight, and most did not feel it was easily calculable with the current electronic medical record system. CONCLUSIONS: Despite a trend toward lower tidal volumes over the years, in 2018, over a quarter of mechanically ventilated adult patients were being ventilated with tidal volumes greater than 8 cc/kg. Survey data indicate that despite respondents acknowledging the benefits of lung-protective ventilation, there are barriers to its optimal implementation. Future modifications of the electronic medical record, including a calculator to set tidal volume in cc/kg and the use of default set tidal volumes, may help facilitate the delivery of and adherence to lung-protective ventilation.

Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype.

Profibrotic cells derived from circulating CD14+ monocytes include fibrocytes and alternatively activated macrophages. These cells are associated with interstitial lung disease (ILD) and are implicated in the pathogenesis of systemic sclerosis (SSc); however, the simultaneous presence of profibrotic cells and their associated mediators in the circulation of these patients has not been defined. We hypothesized that monocytes from patients with SSc-related ILD (SSc-ILD) would show profibrotic characteristics when compared with normal controls. We recruited patients with SSc-ILD (n=12) and normal controls (n=27) and quantified circulating collagen-producing cells by flow cytometry for CD45 and pro-collagen I. The in vitro activation potential of CD14+ monocytes in response to lipopolysaccharide was assessed using flow cytometry for CD163, and by ELISA for CCL18 and IL-10 secretion. Profibrotic mediators in plasma were quantified using Luminex-based assays. The concentration of circulating collagen-producing cells was increased in the SSc-ILD patients when compared with controls. These cells were composed of both CD34+ fibrocytes and a population of CD34+CD14+ cells. Cultured CD14+ monocytes from SSc-ILD patients revealed a profibrotic phenotype characterized by expression of CD163 and by enhanced secretion of CCL18 and IL-10 in response to proinflammatory activation. Plasma levels of IL-10, MCP-1, IL-1RA, and TNF levels were significantly elevated in the plasma of the SSc-ILD cohort. Subgroup analysis of the normal controls revealed that unlike the subjects < or =35 years, subjects > or =60 years old showed higher levels of circulating CD34+CD14+ cells, collagen-producing CD14+ monocytes, CD163+ monocytes, IL-4, IL-10, IL-13, MCP-1, and CCL18. These data indicate that the blood of patients with SSc-ILD and of healthy aged controls is enriched for fibrocytes, profibrotic monocytes, and fibrosis-associated mediators. Investigations defining the factors responsible for this peripheral blood profile may provide new insight into SSc-ILD as well as the pathophysiology of aging.

Development of an Accurate Bedside Swallowing Evaluation Decision Tree Algorithm for Detecting Aspiration in Acute Respiratory Failure Survivors.

BACKGROUND: The bedside swallowing evaluation (BSE) is an assessment of swallowing function and airway safety during swallowing. After extubation, the BSE often is used to identify the risk of aspiration in acute respiratory failure (ARF) survivors. RESEARCH QUESTION: We conducted a multicenter prospective study of ARF survivors to determine the accuracy of the BSE and to develop a decision tree algorithm to identify aspiration risk. STUDY DESIGN AND METHODS: Patients extubated after ≥ 48 hours of mechanical ventilation were eligible. Study procedures included the BSE followed by a gold standard evaluation, the flexible endoscopic evaluation of swallowing (FEES). RESULTS: Overall, 213 patients were included in the final analysis. Median time from extubation to BSE was 25 hours (interquartile range, 21-45 hours). The FEES was completed 1 hour after the BSE (interquartile range, 0.5-2 hours). A total of 33% (70/213; 95% CI, 26.6%-39.2%) of patients aspirated on at least one FEES bolus consistency test. Thin liquids were the most commonly aspirated consistency: 27% (54/197; 95% CI, 21%-34%). The BSE detected any aspiration with an accuracy of 52% (95% CI, 45%-58%), a sensitivity of 83% (95% CI, 74%-92%), and negative predictive value (NPV) of 81% (95% CI, 72%-91%). Using recursive partitioning analyses, a five-variable BSE-based decision tree algorithm was developed that improved the detection of aspiration with an accuracy of 81% (95% CI, 75%-87%), sensitivity of 95% (95% CI, 90%-98%), and NPV of 97% (95% CI, 95%-99%). INTERPRETATION: The BSE demonstrates variable accuracy to identify patients at high risk for aspiration. Our decision tree algorithm may enhance the BSE and may be used to identify patients at high risk for aspiration, yet requires further validation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02363686; URL: www.clinicaltrials.gov.

Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study.

BACKGROUND: An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications. Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy. To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19. METHODS: In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital. Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range. We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes. We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable. We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality. Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival. FINDINGS: 68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls. Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014). VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients. We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients. In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087). INTERPRETATION: Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death. Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19. FUNDING: This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health.

Evaluation of Swallow Function Post-Extubation: Is It Necessary to Wait 24 Hours?

BACKGROUND: Post-extubation dysphagia is associated with an increased incidence of nosocomial pneumonias, longer hospitalizations, and higher re-intubation rates. The purpose of this study was to determine if it is necessary to delay swallow evaluation for 24 hours post-extubation. METHODS: A prospective investigation of swallowing was conducted at 1, 4, and 24 hours post-extubation to determine if it is necessary to delay swallow evaluation following intubation. Participants were 202 adults from 5 different intensive care units (ICU). RESULTS: A total of 166 of 202 (82.2%) passed the Yale Swallow Protocol at 1 hour post-extubation, with an additional 11 (177/202; 87.6%) at 4 hours, and 8 more (185/202; 91.6%) at 24 hours. Only intubation duration ≥4 days was significantly associated with nonfunctional swallowing. CONCLUSIONS: We found it is not necessary to delay assessment of swallowing in individuals who are post-extubation. Specifically, the majority of patients in our study (82.2%) passed a swallow screening at 1 hour post-extubation.

VEGF-induced heme oxygenase-1 confers cytoprotection from lethal hyperoxia in vivo.

Prolonged exposure to hyperoxia results in hyperoxic acute lung injury (HALI). Vascular endothelial growth factor (VEGF) has been shown to have cytoprotective effects and prolong survival in an in vivo model of HALI. Heme oxygenase-1 (HO-1) has protective effects in hyperoxia; therefore, we hypothesized that induction of HO-1 would be an important contributor to VEGF-induced cytoprotection. Using inducible, lung-specific VEGF overexpressing transgenic mice, we demonstrated that VEGF is a potent inducer of HO-1 mRNA and protein in mouse lung. To evaluate the effect of inhibition of HO-1 on injury, VEGF transgenic mice were treated with HO-1 short interfering RNA (HO-1 siRNA) and exposed to hyperoxia. Total lung lavage protein concentration, TUNEL staining, lipid peroxidation, and wet-to-dry ratio were all increased, consistent with increased injury. These findings were corroborated by survival studies in which inhibition of HO-1 function using tin-protoporphryin or silencing of HO-1 with lentiviral HO-1 short hairpin RNA (ShRNA) significantly decreased survival in hyperoxia. We conclude from these data that VEGF-induced HO-1 is an important contributor to cytoprotection in this in vivo model of acute lung injury and that alterations in VEGF function in the lung are likely to be important determinants of the outcome of acute lung injury.

Mechanical ventilation and acute respiratory distress syndrome in older patients.

As the population of the United States ages, an increasing number of elderly adults will be cared for in intensive care units. An understanding of how aging affects the respiratory system is important for patient care and ongoing research. The incidence rates of acute respiratory failure and of acute respiratory distress syndrome increase dramatically with age, and therefore understanding the relationship between age and ARDS is important. This article focuses on the age-specific changes in respiratory function. We present a discussion of the management of acute lung injury and acute respiratory distress syndrome with a focus on the role of mechanical ventilation. We conclude with what is known about age and its impact on mortality and functional outcomes after mechanical ventilation.