Onset Of Adult Respiratory Distress Syndrome Research Articles

Hypoalbuminemia: incidence and its impact on acute respiratory distress syndrome and 28-day outcome in trauma patients.

This prospective observational study explored the effect of early onset hypoalbuminemia (EOH) on the development of adult respiratory distress syndrome (ARDS) in orthopedic trauma victims. Serum albumin levels were measured for the initial 7days of injury for adult trauma patients (18-65years). Patients were recruited into group A (any serum albumin value < 3.5mg/dl) and group B (all serum albumin ≥ 3.5mg/dl), based on serum albumin values. Patients were followed for the development of ARDS and outcome until 28days. The primary outcome of the study was to explore the effects of EOH on ARDS. EOH (any serum albumin value < 3.5g/dl within 7days of injury) was present in 205/386 (53.1%) patients. The majority of 174/205 (84.9%) patients had EOH by the fourth day after the injury, with the mean time for development of EOH being 2.15 ± 1.87days. ARDS manifested in 87/205 (42.4%) and 15/181 (8.3%) patients in group A and group B, respectively (p < 0.001). EOH had 8.2 times greater odds of ARDS (OD 8.2 95% CL 4.7-14.0, p = 0.000). The mean time for the onset of ARDS was 5.63 ± 2.62days. No statistically significant causal relationship occurred between the onset of EOH and the development of ARDS (Pearson's correlation coefficient = 0.14, p = 0.16). At serum albumin cutoff concentrations of 3.4 gm/dl on D1 (AUC 0.68, 95% CI: 0.61-0.74, p = 0.000), ARDS may be anticipated in 62.8% of patients. The commencement of ARDS was independently correlated with EOH (p = 0.000), Respiratory rate on admission (p = 0.000), inotrope use (p = 0.000), and soft tissue injury (p = 0.000) (R2 = 0.466). The odds of 28-day all-cause death were 7.7 times higher in EOH (OD 7.7 95% CL 3.5-16.7, p = 0.00) and 9 times higher in ARDS (OD 9 95% CL 4.9-16.16, p = 0.00). EOH is a frequent occurrence and has a strong influence development of ARDS and 28-day mortality in trauma patients.

Lung Transplantation for COVID-19-related Lung Disease: Clinical Experience and Call for a Global Registry.

Lung Transplantation for COVID-19-related Lung Disease: Clinical Experience and Call for a Global Registry.

Early initiation of extracorporeal membrane oxygenation improves survival in adult trauma patients with severe adult respiratory distress syndrome.

The use of extracorporeal membrane oxygenation (ECMO) in the trauma population has been reported to have a mortality benefit in patients with severe refractory hypoxic respiratory failure. This study compares the early initiation of ECMO for the management of severe adult respiratory distress syndrome (ARDS) versus a historical control immediately preceding the use of ECMO for trauma patients. A retrospective study was conducted at a single verified Level I trauma center. The study population was limited to trauma patients diagnosed with severe ARDS using the Berlin definition (PaO2/FIO2 ratio < 100). Patients managed with ECMO versus conventional ventilation (CONV) were compared. The primary outcome of interest was mortality; secondary outcomes included hospital length of stay, intensive care unit-free days, and ventilator-free days. Fifteen ECMO patients managed from March 2013 to November 2014 were identified, as were 14 CONV patients managed from March 2012 to February 2013 who met the Berlin definition of severe ARDS. Data related to age, Injury Severity Scores (ISSs), admission lactic acid levels, base deficit, the number of transfused red blood cell units within the first 24 hours, and presence of severe traumatic brain injury were collected and were not statistically different between the groups. Likewise, Murray Lung Injury (MLI), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores determined at the onset of severe ARDS were not statistically different between the groups. Median hospital stay (CONV, 28.0 days [14.0-47.0]; ECMO, 43.5 days [30.0-93.0]; p = 0.15), intensive care unit-free days (CONV, 0.0 days [0.0-5.0]; ECMO, 5.0 days [0.0-7.0]; p = 0.26), and ventilator-free days (CONV, 0.0 days [0.0-10.0]; ECMO, 8.0 days [0.0-19.0]; p = 0.13) were not statistically different between the groups. Mortality in the ECMO group was significantly reduced compared with the CONV group (ECMO, 13.3%; CONV, 64%; p = 0.01). Timing from the onset of severe ARDS to ECMO intervention occurred at a mean 1.9 ± 1.4 days. Patients who were treated with ECMO for severe ARDS had an improved mortality compared with historical controls. ECMO should be considered at the early onset of severe ARDS to improve survival. Therapeutic study, level IV.

Lung CT Scan

In the last 20 years, the use of computed tomography (CT) to evaluate thoracic diseases has rapidly gained popularity and CT has become firmly established as an important research and diagnostic modality. In particular, CT has played an important role in improving our knowledge about the pathophysiology of the adult respiratory distress syndrome (ARDS) and in determining the morphological and functional relationships of different therapeutic options commonly used in the clinical management of this syndrome. CT scan may provide: 1) accurate measurement of the impact of mechanical ventilation on hyperaeration and reaeration/recruitment, being the most objective technique currently available to set mechanical ventilation and identifying patients for extracorporeal lung support; 2) the amount of lung edema, associated with the severity of the alveolar capillary barrier lesion and the risk of mortality; 3) clinical information in patients with a sudden and unexplained deterioration of the clinical status or the lack of expected improvement as well as to follow the evolution with time. We recommend to perform: 1) one single whole lung CT scan at end-expiration at PEEP 5 cmH2O, to evaluate the distribution of aeration and to compute the amount of lung weight; 2) only three lung CT slices, taken at the lung apex, hilum, and basis, at PEEP = 5 cmH2O and at Pplat = 45 cmH2O, to assess of lung recruitability; 3) a CT scan as early as possible after onset of ARDS (if clinical characteristics persist for more than 24 hours) and repeat it after 1 week if no clinical improvement is observed; 4) a CT scan in presence of any clinical deterioration not explained by conventional diagnostic tools. We suggest considering the measurement of extravascular lung water and end-expiratory lung volume by non radiological techniques and lung ultrasound if CT scan cannot be done.

Interleukin-8, aquaporin-1, and inducible nitric oxide synthase in smoke and burn injured sheep treated with percutaneous carbon dioxide removal.

We previously showed that a percutaneous arteriovenous gas exchanger was effective in removing CO2 and reversing respiratory failure in an ovine model of adult respiratory distress syndrome (ARDS) produced by smoke inhalation and burn injury (Alpard et al., Ann Surg 230:215-224, 1999). In this study, we tested the hypothesis that arteriovenous CO2 removal (AVCO2R) lessened endogenous inflammation in the lung. Myeloperoxidase activity, aquaporin-1 (AQP-1), interleukin-8 (IL-8), and inducible nitric oxide synthase mRNAs as well as aquaporin-1, and IL-8 protein were measured in ovine lung tissue. Lung tissue was taken at 96 h (time of sacrifice) from animals with combined smoke inhalation and 40% third degree dermal burn and subsequently treated with AVCO2R or sham (ventilator alone) after onset of ARDS (PaO2:FiO2 ratio of < 200). Myeloperoxidase activity was 1.862 +/- 0.302 U/mg protein in the ventilator group and 0.830 +/- 0.141 in the AVCO2R plus ventilator group. AQP-1 mRNA was 140,482 +/- 31,702 copies/microg total RNA in the ventilator group and 61,854 +/- 22,433 copies/microg total RNA in the AVCO2R plus ventilator group (p = 0.076). mRNA for IL-8 mRNA in the ventilator alone treated animals was 74,000 +/- 3,300 copies/microg total RNA compared to < 1,000 copies/microg total RNA in the ventilator plus AVCO2R group. This result was highly significant (p < 0.001) Inducible nitric oxide synthase mRNA was 7,853 +/- 2,229 copies/microg total RNA for the AVCO2R group and 5,854 +/- 2,070 copies/microg total RNA for the ventilator managed animals. These differences were not statistically significant (p = 0.54). Percutaneous AVCO2R produced a specific decrease in IL-8 in the smoke and burn injured animals. Furthermore, this effect was consistent with cell signaling mechanisms that increase the expression of IL-8 by cyclic stretching and the observed reduction in the number of neutrophils in the lung parenchyma. Therefore, we speculate that the mechanism by which CO2 removal exerts a beneficial effect may be due to both decreases in ventilatory requirements, with an accompanying reduction in alveolar stretching, and reduction of neutrophil numbers in lung tissue.

Hemodynamic stability during arteriovenous carbon dioxide removal for adult respiratory distress syndrome: a prospective randomized outcomes study in adult sheep.

To evaluate the ability of arteriovenous carbon dioxide removal (AVCO2R) to maintain hemodynamic stability during treatment of adult respiratory distress syndrome (ARDS), we used our smoke/burn, LD40 sheep model of ARDS. With onset of ARDS (PaO2/FiO2 < 200) animals were randomized to AVCO2R (n = 20) or SHAM (n = 8). With AVCO2R, the carotid artery (10-14 F) and jugular vein (14-16 F) were cannulated; SHAM received identical management, sparing the vessels. AVCO2R maintained stable hemodynamics compared to SHAM at 48 hours; heart rate (114.8+/-6.1 vs. 110.1+/-11.0 beats/min.), mean arterial pressure (112+/-5.1 vs. 107.0+/-8.5 mm Hg), cardiac output (7.4+/-0.5 vs. 7.5+/-0.9 L/min.), pulmonary arterial pressure (26+/-2.4 vs. 21+/-1.3 mm Hg), pulmonary arterial wedge pressure (14.1+/-1.8 vs. 14.0+/-1.2 mm Hg), and central venous pressure (7+/-1.6 vs. 8+/-0.9 mm Hg). At 48 hours, AVCO2R allowed significant reductions (p<0.05) in minute ventilation (13.6+/-2.5 to 7.6+/-0.8 L/min); tidal volume (TV) (389.4+/-24.1 to 295.0+/-10.1 ml); peak inspiratory pressure (PIP) (25.4+/-9.2 to 18.8+/-2.5 cm H2O); RR (27.5+/-0.7 to 21.6+/-1.8 breaths/min); and FiO2 (0.96+/-0.00 to 0.48+/-0.2) while normocapnia was maintained. AVCO2R is an effective method of CO2 removal during severe respiratory failure that is hemodynamically well tolerated.

A 9-year, single-institution, retrospective review of death rate and prognostic factors in adult respiratory distress syndrome.

To evaluate, at a single institution, the adult respiratory distress syndrome (ARDS) death rate in critically ill ventilated surgical/trauma patients and to identify the factors predicting death in these patients. The prognostic features affecting mortality at the onset of ARDS have not been clearly defined. Defining rare characteristics would be valuable because it would allow for better stratification of patients in clinical trials and more appropriate utilization of constrained resources in ICU environments. A retrospective analysis of 980 ventilated surgical and trauma intensive care unit patients from January 1990 to December 1998 was performed at Rhode Island Hospital. One hundred eleven adult intensive care unit patients with ARDS were identified using the criteria of Lung Injury Score more than 2.50 and the definition from the American-European Consensus Conference. Slightly more than half were trauma patients, 57% were men, and the median age was 59 years. The overall death rate was 52%. Patients were segregated by admission date to the intensive care unit (before or after January 1, 1995). Severity of illness was measured by the Revised Trauma Score for trauma patients and the Acute Physiology and Chronic Health Evaluation III for surgical patients. The Multiple Organ Dysfunction Score was determined on the day of onset of ARDS for all patients. Other recorded variables were age, sex, intensive care unit length of stay, length and mode of ventilation, presence or absence of tracheostomy, ventilation variables of peak and mean airway pressures, lung injury scores, elective versus emergency surgery, and presence or absence of pneumonia. There was a significant decrease in the ARDS death rate from the period 1990 to 1994 to the period 1995 to 1998. The major reason for the decline was a reduction in the posttraumatic ARDS death rate. Lung-protective ventilation strategies were used more frequently in the second period than in the first, and the death rate was significantly decreased in trauma patients in the second period when lung-protective ventilation modes were used. Predictors of death at the onset of ARDS were advanced age, Multiple Organ Dysfunction Score of 8 or more, and Lung Injury Score of 2.76 or more. In this single-institution series, the death rate from ARDS declined from 1990 to 1998, primarily in posttraumatic patients, and the decrease is related to the use of lung-protective ventilation strategies. Based on this patient population, the authors developed a statistical model to evaluate important prognostic indicators (advanced age, organ system and pulmonary dysfunction measurements) at the onset of ARDS.

ARDS in patients with thermal injury.

To determine the time to onset of the adult respiratory distress syndrome (ARDS) in patients with thermal injury requiring mechanical ventilation. Secondarily, to consider the burn-related risk factors, demographics, incidence, and mortality for ARDS in this population. Retrospective chart review; ARDS defined according to the American-European Consensus Conference and the Lung Injury Severity Score definitions. Regional, tertiary referral, adult burn unit in a university teaching hospital. Patients with thermal injury requiring mechanical ventilation, admitted between 1 January 1991 and 28 February 1995. None. Of 469 consecutive admissions, 126 (26.9%) received intubation and mechanical ventilation. ARDS was defined according to the American-European Consensus and Lung Injury Severity Score (score > 2.5) definitions. The mean time to onset of ARDS from admission to the burn unit was 6.9 +/- 5.2 and 8.2 +/- 10.7 days when defined by the American-European Consensus and Lung Injury Severity Score definitions respectively (p = 0.41). Of the intubated patients, 53.6 and 45.2% developed ARDS according to the American-European Consensus and Lung Injury Severity Score definitions, respectively (p = 0.19). Using multivariate logistic analysis, only age proved to be an independent risk factor for the development of ARDS (p = 0.03), although there was a trend toward an increased incidence of inhalation injury in patients with ARDS. Mortality was not significantly greater (41.8 vs 32.2%) in those with ARDS compared to those without (p = 0.27). According to the American-European Consensus Conference and the Lung Injury Severity Score definitions, ARDS is common in the adult burn population and has a delayed onset compared to most critical care populations. We found age to be a major predisposing factor for ARDS.

Adult respiratory distress syndrome in systemic lupus erythematosus: causes and prognostic factors: a single center, retrospective study.

To determine the causes and prognostic factors of Adult Respiratory Distress Syndrome (ARDS) in patients with systemic lupus erythematosus (SLE). Among 544 Korean SLE patients, who were followed in the Lupus Clinic of the Catholic Medical Center from 1993 to 1997, patients diagnosed as ARDS were examined retrospectively. During the study period, non-SLE patients with ARDS were investigated and then compared to SLE patients with ARDS in terms of clinical variables. Nineteen patients with SLE were revealed to have a history of ARDS (3.5%) and 13 (68.4%) of 19 patients died. Death related to ARDS was found in 34.2% of all deaths (n=38) from SLE during the study period. The frequency and causes of ARDS were as follows; 9 sepsis or bacteremia (47.4%), 2 miliary tuberculosis (10.5%), 2 invasive pulmonary aspergillosis (10. 5%), 2 acute pulmonary alveolar hemorrhage syndrome (10.5%), 1 acute lupus pneumonitis (5.3%), 1 massive hemorrhage due to placenta previa (5.3%), 1 aspiration pneumonitis (5.3%), 1 disseminated intravascular coagulation associated with systemic vasculitis (5.3%). The main organisms in sepsis were gram negative bacilli (61.5%) The median steroid dose administered 1 month before ARDS was significantly higher in patients (n=13) with infectious ARDS compared to those (n=6) with ARDS due to other causes (P=0.038). Comparison of the laboratory and clinical variables between the survivors (n=6) and the deceased (n=13) showed that the survivors had lower SLAM indices at presentation (P=0.004) and APACHE (Acute Physiology, Age, Chronic Health Evaluation) III scores within 24 h after diagnosis of ARDS (P=0.024) than the deceased. The APACHE III scores correlated well with the SLAM indices (r=0.615, P=0.007). Non-SLE patients with ARDS during the study period were selected for comparison to SLE patients with ARDS. Age at the onset of ARDS was younger in SLE (n=19) compared to non-SLE (n=190) (P<0.001). Duration from ARDS onset to death was shorter in SLE patients (P<0. 001). The mortality from ARDS tended to be higher in SLE patients (P=NS). The first-day APACHE III score was significantly higher in deceased SLE patients (n=13) compared to deceased non-SLE patients (n=105) (P=0.001). ARDS was a common premortem event of SLE and showed a high fatality rate in SLE. The most common cause of ARDS in Korean patients with SLE was sepsis by gram negative bacilli. ARDS in SLE developed at a younger age, and progressed more rapidly compared to ARDS in general. The SLAM index and APACHE III score could be useful to predict the prognosis of ARDS in SLE.

Ventilator-associated pneumonia in patients with adult respiratory distress syndrome: CT evaluation.

To determine the diagnostic accuracy of computed tomography (CT) for pneumonia in patients with adult respiratory distress syndrome (ARDS). CT scans were obtained within 1 week of bronchoscopic sampling in 31 patients receiving mechanical ventilation for ARDS for more than 48 hours. Of 11 patients with pneumonia, five developed symptoms less than 11 days after the onset of ARDS (early ARDS). CT scans were rated for pneumonia independently by four radiologists who were unaware of the clinical diagnosis. Diagnostic accuracy was defined by means of the area under the receiver operating characteristic curve, or A2. Diagnostic accuracy for pneumonia was fair (A2 = 0.69 +/- 0.04 [standard error]) owing to 70% true-negative ratings (vs 59% true-positive ratings). The generalizability coefficient was good (0.79). No single CT finding was significantly different for the presence of pneumonia. Nondependent opacities predominated in 10 (91%) of 11 patients with pneumonia and 12 (60%) of 20 without pneumonia. Nondependent opacities predominated in nine (56%) of 16 patients with early ARDS and 13 (87%) of 15 with late ARDS. CT has fair diagnostic accuracy for ventilator-associated pneumonia in patients with ARDS owing primarily to identification of patients without pneumonia. No single CT sign was significantly different for pneumonia, but dependent atelectasis was more common in patients with early ARDS without pneumonia.

Lower respiratory tract colonization and infection during severe acute respiratory distress syndrome: incidence and diagnosis.

Ventilator-associated pneumonia (VAP) is difficult to detect and is often unsuspected during adult respiratory distress syndrome (ARDS). We prospectively evaluated lower respiratory tract (LRT) colonization and infection in 30 patients with severe ARDS (PaO2/FIO2 ratio < 150 mm Hg), using repeated quantitative cultures of plugged telescopic catheter (PTC) specimens taken blindly via the endotracheal tube every 48 to 72 h after onset of ARDS. All patients except one were receiving antibiotics. When VAP was suspected on the presence of clinical criteria for infection, a repeated PTC and, when possible, a bronchoalveolar lavage (BAL) were obtained before any new antimicrobials were administered; samples growing > or = 10(3) cfu/ml (PTC) or > or = 10(4) cfu/ml (BAL) were considered diagnostic of infection. Twenty-four VAP episodes were diagnosed in 18 patients (60% of patients or 4.2/100 ventilator-days) a mean of 9.8+/-5.7 d after onset of ARDS. Eighteen LRT colonization episodes were recorded; 16 of 24 (66%) VAP episodes were preceded (by 2 to 6 d) by LRT colonization with the same organism(s), and only two episodes of colonization were not followed by VAP. We conclude that although VAP is of relatively late-onset during severe ARDS, its incidence is much higher than in other conditions and can be underestimated. Lower airways colonization is consistently followed by infection with the same organisms and precedes VAP in two thirds of episodes. Repeated protected specimens taken blindly may provide a useful means to predict infection and therefore allow early antimicrobial therapy in high-risk patients with diffuse lung injury.

Adult respiratory distress syndrome associated with epidural fentanyl infusion

Objective: To determine the cause of unexplained postoperative adult respiratory distress syndrome (ARDS). Design: Case-control study of postoperative ARDS. Setting: Intensive care unit (ICU) of a Veterans Affairs hospital. Patients: Six postoperative patients recovering from uncomplicated vascular or cardiothoracic surgery developed unexplained ARDS. Controls were 17 patients having similar procedures without the development of ARDS. Intervention: Infusion of fentanyl with a tamper-proof device. Measurements and Main Results: Development of ARDS. ARDS began 1 to 4 days after surgery, was characterized by maximum alveolar-arterial oxygen gradient that ranged from 232 to 544 torr (30.9 to 72.5 kPa), and was associated with death of two patients. We observed no association with patient location before ARDS onset, nonanalgesic medication administered, staff assignment, or mode of respiratory therapy. All six patients who developed unexplained ARDS had received epidural fentanyl compared with none of 17 control patients without ARDS (p= .0002). We instituted a tamper-proof mode of parenteral fentanyl administration, and subsequently observed one case of ARDS in 26 consecutive surgical patients (p= .000014). Conclusions: Based on these findings, as well as a prior history of fentanyl theft at our institution, we conclude that tampering with fentanyl infusate was responsible for the ARDS epidemic that we observed. (Crit Care Med 1994; 22:1579–1583)

Adult respiratory distress syndrome associated with epidural fentanyl infusion

To determine the cause of unexplained postoperative adult respiratory distress syndrome (ARDS). Case-control study of postoperative ARDS. Intensive care unit (ICU) of a Veterans Affairs hospital. Six postoperative patients recovering from uncomplicated vascular or cardiothoracic surgery developed unexplained ARDS. Controls were 17 patients having similar procedures without the development of ARDS. Infusion of fentanyl with a tamper-proof device. Development of ARDS. ARDS began 1 to 4 days after surgery, was characterized by maximum alveolar-arterial oxygen gradient that ranged from 232 to 544 torr (30.9 to 72.5 kPa), and was associated with death of two patients. We observed no association with patient location before ARDS onset, nonanalgesic medication administered, staff assignment, or mode of respiratory therapy. All six patients who developed unexplained ARDS had received epidural fentanyl compared with none of 17 control patients without ARDS (p = .0002). We instituted a tamper-proof mode of parenteral fentanyl administration, and subsequently observed one case of ARDS in 26 consecutive surgical patients (p = .000014). Based on these findings, as well as a prior history of fentanyl theft at our institution, we conclude that tampering with fentanyl infusate was responsible for the ARDS epidemic that we observed.

Pulmonary Endothelial Permeability in Patients With Severe Lung Injury: Clinical Correlates and Natural History

To establish the natural history of lung injury in adult respiratory distress syndrome (ARDS) in terms of increased pulmonary vascular permeability. Secondly, to relate such changes to the number of neutrophils in bronchoalveolar lavage (BAL) and a clinical score of the severity of lung injury. Prospective, open. Adult intensive care unit of a tertiary (national) referral hospital. Fourteen patients meeting accepted diagnostic criteria for ARDS. Mechanical ventilatory support. Conventional intensive care and support for other failed organ systems as appropriate. Pulmonary vascular permeability was estimated using a dual isotope technique (protein accumulation index [PAI]), neutrophil numbers by BAL and the severity of ARDS by the lung injury score (LIS). The PAI and LIS were measured simultaneously on three occasions as far apart as possible during the course of the illness. A single BAL was performed immediately after one of the three PAI/LIS measurements, the precise timing being dictated by the clinical stability of each patient. Fourteen patients (8 male; age range, 19 to 69 years) were studied, 1.40 +/- 0.16, 11.36 +/- 1.79, and 20.90 +/- 2.30 days after the onset of ARDS (mean +/- SEM). Six patients died. The PAI (normal range, 0 to 1.0 x 10(-3)) was 2.81 +/- 0.39, 2.94 +/- 0.48, and 2.80 +/- 0.87; and LIS (severe injury > or = 2.5) was 2.18 +/- 0.25, 2.48 +/- 0.14, and 2.06 +/- 0.27, respectively. The BAL neutrophil content was 54.09 +/- 8.89. There were significant positive correlations between PAI and LIS (r = 0.73, p < 0.001) and PAI and BAL neutrophil content (r = 0.81, p < 0.001). These data suggest that increased pulmonary vascular permeability persists throughout the course of ARDS and is related to a clinical score of injury severity and BAL neutrophil content.

Evolution of bronchoalveolar cell populations in the adult respiratory distress syndrome.

To characterize the evolution of inflammation in the adult respiratory distress syndrome (ARDS) and test the hypothesis that sustained alveolar inflammation is associated with a poor outcome in patients with ARDS, we performed fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) in 125 patients and compared BAL cells and protein concentrations in survivors and nonsurvivors. ARDS followed sepsis syndrome in 35 patients, major trauma in 41, and other causes in 49. When possible, BAL was performed on Days 3, 7, and 14 after the onset of ARDS. Sixty-five patients (52%) had more than one BAL. We first performed analyses on each BAL day using information from all 212 BAL in the 125 patients (cross-sectional analysis). All patients had increased leukocytes and total protein in the first BAL (Day 3 after onset of ARDS). In patients with ARDS following sepsis, the percentage of BAL polymorphonuclear leukocytes (PMN) was higher on Day 7 (p = 0.11) and particularly Day 14 (p = 0.02) in patients who died; there was a consistent trend of a higher PMN concentration on all days in patients who died then in those who lived. In patients with ARDS following trauma and other risks, however, BAL PMN measures did not distinguish survivors from patients who died. Analysis of serial data from the patients with more than one BAL showed that alveolar macrophages (AM) increased in survivors of ARDS, both in absolute numbers and as a percentage of total cells; this pattern was most pronounced in the sepsis patients. The cross-sectional data analysis suggests that sustained alveolar inflammation occurs frequently in patients with ARDS following sepsis and is associated with a high mortality.

CD11b/CD18 expression, adherence, and chemotaxis of granulocyte in adult respiratory distress syndrome.

The accumulation of granulocytes in the pulmonary microvasculature is generally thought a cardinal event in the pathology of adult respiratory distress syndrome (ARDS). However, the mechanism by which granulocytes are sequestered in the pulmonary vascular bed remains largely unknown. Because the CD11b/CD18 membrane receptors mediate various adhesion-dependent functions, their expression was investigated in granulocytes from patients during the course of ARDS development in relation to adherence and chemotaxis. CD11b expression of ARDS resting granulocytes was increased within 24 h of ARDS onset by a factor of two in comparison with control patients (p < 0.05) and remained significantly increased 72 to 120 h later. In contrast, the stimulated expression was significantly decreased only within 24 h of ARDS onset. Adherence was not modified within 8 h of the onset of ARDS, but was increased at Days 1, 3, and 5. The time course of granulocyte chemotaxis shows a decreased chemotaxis capacity during the first 3 d of ARDS, followed by normalization at Day 5. The dynamic changes observed in the various functions studied indicate a possible relationship between the modulation of the CD11b expression and a hyperadhesive state of granulocytes in ARDS. These sticky granulocytes may potentially contribute to the microvascular injury.

Temporal patterns of hemodynamics, oxygen transport, cytokine activity, and complement activity in the development of adult respiratory distress syndrome after severe injury.

The aim of this study was to search for early inflammatory mediators in severely traumatized patients that could predict the occurrence of adult respiratory distress syndrome (ARDS). We measured sequential plasma levels of tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 8 (IL-8), complement fragment C3a, and endotoxin. In addition, we measured sequentially the values of hemodynamics, oxygen transport, and pulmonary function. The temporal patterns seen in the patients who developed ARDS were compared with those who did not. In the patients who developed ARDS, the first observed findings were low cardiac index (CI) and oxygen delivery (DO2) followed by progressive increases in IL-6, IL-8 and C3a levels, worsening of pulmonary function, and increases in hemodynamic values. The maximum values of IL-6, IL-8, and C3a occurred after the onset of ARDS. In the patients who did not develop ARDS, initial oxygen transport values were not low, the levels of IL-6, IL-8, and C3a decreased rapidly from their initial peaks, and there were no further increases in hemodynamic values. In both ARDS and nonARDS patients, no measurable quantities of TNF, IL-1, or endotoxin were found. We concluded that none of the mediators we measured reached their peaks before the onset of ARDS and none were found to be predictive of posttraumatic ARDS. However, these and other mediators may augment or intensify the development of ARDS.

Temporal patterns of radiographic infiltration in severely traumatized patients with and without adult respiratory distress syndrome.

We prospectively evaluated the patterns of pulmonary structural and functional changes in 100 consecutive surgical intensive care unit trauma patients who had (1) emergent major surgery, (2) a pelvic fracture, or (3) two or more major long bone fractures. For each patient, arterial blood gas measurements (ABGs), central venous pressure (CVP), pulmonary capillary occlusion pressure (PAOP), thoracic compliance, arterial oxygen tension/fraction of inspired oxygen (PAO2/FIO2), pulmonary venous admixture (Qs/Qt), and portable chest roentgenograms were sequentially tracked. The senior staff radiologist interpreted all chest roentgenograms. Pulmonary infiltration was quantitated in each of six fields using a scale ranging from 0 to 4, with 0 being no infiltration and 4 being the maximum. Adult respiratory distress syndrome (ARDS) was defined as follows: Qs/Qt > or = 20%, PAO2/FIO2 < 250 or both; dependence on mechanical ventilation for life support for > or = 24 hours; PAOP or CVP or both < 20 mm Hg; and thoracic compliance < 50 mL/cm H2O. Time zero (T0) the time of onset of ARDS, was defined as the time these criteria were met. Eighty-three of 100 study group patients had penetrating injuries, and 17 were admitted with blunt trauma. Fifty-one of 100 patients developed ARDS: 36 of 51 died. Only 4 of 49 (8%) patients without ARDS died. The injured lungs of patients with and without ARDS had similar amounts of infiltration over most measured time intervals. The noninjured lungs of the ARDS patients, however, had significantly greater infiltration than those without ARDS at T0 and over subsequent time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Effects of a Single Dose of Porcine Surfactant on Patients With the Adult Respiratory Distress Syndrome

In an attempt to restore functional surfactant to the lungs of patients with the adult respiratory distress syndrome (ARDS), we have treated six patients within the first 2 days of the onset of ARDS with a single dose of hydrophobic components of porcine surfactant. Surfactant (4 g in 50 ml) delivered via a bronchoscope in aliquots to each of the lobar bronchi was well tolerated and caused a modest transient improvement in gas exchange. No significant changes in chest radiograph or lung compliance were detected. Analysis of bronchoalveolar lavage (BAL) fluid showed no change in albumin, alpha-1-proteinase inhibitor specific activity, or cell count. Bronchoalveolar lavage phospholipid concentrations were elevated 3 h after surfactant administration relative to preadministration levels and fell by 24 h. In addition, in two patients we found reduced inhibition of surfactant function in BAL after surfactant replacement. These observations suggest a role for surfactant replacement in the treatment of patients with ARDS and support the need for continuing investigation.

Serial Measurements of Plasma Elastase α1-Proteinase Inhibitor Complexes in Patients Receiving Cancer Chemotherapy

We monitored the plasma elastase:alpha 1-proteinase inhibitor complexes during chemotherapy for cancer and investigated the relationship between the elastase burden and the onset of adult respiratory distress syndrome (ARDS) in 20 patients with primary lung cancer who received combination chemotherapy; 15 normal nonsmokers served as controls. Of the 20 patients, 6 developed pneumonia, and 6 developed ARDS. We measured peripheral WBCs, C-reactive protein (CRP), plasma elastase:alpha 1-proteinase inhibitor complex (complex), and the ratio of complex/WBC during chemotherapy for cancer. In patients who did not experience complications during combination chemotherapy, WBC counts changed, but levels of complex were normal. In patients who developed pneumonia, levels of complex were abnormally high during the WBC nadir, and the complex/WBC count increased along with the level of CRP. In patients who developed ARDS during chemotherapy for cancer, levels of complex were abnormally high immediately after chemotherapy and remained high after the onset of ARDS. In addition, complex/WBC counts and CRP levels increased at the onset of ARDS. The maximum complex concentration was significantly higher in patients with pneumonia (414.3 +/- 57.2 ng/ml) and ARDS (683.2 +/- 72.8 ng/ml), compared with normal nonsmokers (130.2 +/- 5.5 ng/ml; p < 0.01) and patients who did not develop complications (211.5 +/- 23.3 ng/ml; p < 0.01). The maximum complex/WBC count was also significantly higher in patients with pneumonia (0.56 +/- 0.12) and ARDS (1.03 +/- 0.27), compared with normal nonsmokers (0.03 +/- 0.002; p < 0.01) and patients without complications (0.09 +/- 0.01; p < 0.01). These findings suggested a possible correlation between increased levels of complex and the onset of ARDS.