Adult Respiratory Distress Syndrome Group Research Articles

Risk factors of novel severe influenza A(H1N1) with concurrent adult respiratory distress syndrome

To analyze the risk factors of novel severe influenza A (H1N1) with concurrent adult respiratory distress syndrome (ARDS). A multivariable Logistic regression analysis was conducted for ARDS risk factors in controlled clinical trials for comparing the clinical features between the ARDS and non-ARDS groups and comparing ARDS patients' lymphocyte counts and T lymphocyte subsets between the smoking and non-smoking groups through a retrospective analysis of 92 novel influenza A (H1N1) patients who admitted to our hospital from October 2009 to January 2010. Through a single factor analysis between ARDS and non-ARDS groups, the comparisons in the factors including smoking (17 cases vs 11 cases), T lymphocyte subsets, lactate dehydrogenase (LDH), initial treatment point of oseltamivir and initial oxygen flow greater than 2 L/min (28 cases vs 18 cases) had statistically significant differences (all P<0.05). The comparison in T lymphocyte subsets had statistically significant difference between the smoking and non-smoking groups in ARDS patients (all P<0.05). The multivariable Logistic regression analysis showed that smoking (P=0.027, OR=8.05, 95%CI: 1.28-50.80) and initial oxygen flow greater than 2 L/min (P=0.010, OR=16.70, 95%CI: 3.29-84.84) were relevant to the incidence of ARDS in novel influenza A (H1N1) patients. Smoking and initial oxygen flow greater than 2 L/min were the risk factors of novel severe influenza A (H1N1) with concurrent ARDS.

Extracorporeal life support for children with meningococcal septicaemia

Objective To describe the short-term outcome of children with meningococcal sepsis treated with extracorporeal membrane oxygenation (ECMO) in a single centre. Design Retrospective analysis of case notes. Setting The Heartlink ECMO Centre, Glenfield Hospital, Leicester. Patients Eleven children (8 boys) out of a total caseload of 800 patients were treated for meningococcal sepsis with ECMO. Interventions Extracorporeal membrane oxygenation. Results All children with meningococcal sepsis treated with ECMO had a Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) > or = 12 (positive predictive risk of death of approximately 90%). Five children had adult respiratory distress syndrome (ARDS) and six had refractory shock with multi-organ dysfunction syndrome (MODS) at presentation for ECMO. All five children in the ARDS group survived, four of five receiving veno-venous (VV-) ECMO therapy. In contrast, only one of six children with refractory shock with MODS survived, all of whom required veno-arterial (VA-) ECMO therapy. Conclusions Most children with meningococcal sepsis and severe ARDS can be successfully treated with VV-ECMO. In contrast, children with refractory shock and MODS die despite treatment with VA-ECMO. This report does not resolve whether ECMO therapy offers any advantage over conventional therapy in treating severe meningococcal sepsis.

Extracorporeal life support for children with meningococcal septicaemia

To describe the short-term outcome of children with meningococcal sepsis treated with extracorporeal membrane oxygenation (ECMO) in a single centre. Retrospective analysis of case notes. The Heartlink ECMO Centre, Glenfield Hospital, Leicester. Eleven children (8 boys) out of a total caseload of 800 patients were treated for meningococcal sepsis with ECMO. Extracorporeal membrane oxygenation. All children with meningococcal sepsis treated with ECMO had a Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) > or = 12 (positive predictive risk of death of approximately 90%). Five children had adult respiratory distress syndrome (ARDS) and six had refractory shock with multi-organ dysfunction syndrome (MODS) at presentation for ECMO. All five children in the ARDS group survived, four of five receiving veno-venous (VV-) ECMO therapy. In contrast, only one of six children with refractory shock with MODS survived, all of whom required veno-arterial (VA-) ECMO therapy. Most children with meningococcal sepsis and severe ARDS can be successfully treated with VV-ECMO. In contrast, children with refractory shock and MODS die despite treatment with VA-ECMO. This report does not resolve whether ECMO therapy offers any advantage over conventional therapy in treating severe meningococcal sepsis.

Effects of PEEP on inspiratory and expiratory mechanics in adult respiratory distress syndrome

The purpose of the present study was to assess the mechanical behavior of the respiratory system separately during inspiration and expiration in adult respiratory distress syndrome (ARDS) and the influence of PEEP on any phasic variations of the mechanical respiratory parameters. Airways pressure ( P), flow ( V′), and volume ( V) signals were recorded in nine patients with ARDS and 10 patients without known respiratory disorder (control group). All patients were artificially ventilated at three levels of positive end-expiratory pressure (PEEP): 0, 5, and 10 hPa. Data were analyzed separately for inspiratory and expiratory records using multiple linear regression analysis (MLRA) according to the equation: P=Ers V+Rrs V′+ P 0, where Ers and Rrs represent, respectively, the intubated respiratory system elastance and resistance, and P 0 the end-expiratory pressure. In the ARDS group expiratory Ers (Ers EXP=45.58±4.24 hPa/L) was substantially higher ( p<0.01) than inspiratory Ers (Ers INSP=36.76±2.55) with a marked effect of applied PEEP in diminishing the difference between Ers EXP and Ers INSP ( p<0.01). For the ARDS group inspiratory Rrs (Rrs INSP) decreased significantly with increasing PEEP (PEEP=0: Rrs INSP=16.43, PEEP=10: Rrs INSP=13.28, p<0.01). The found differences between Ers EXP and Ers INSP could be attributable to an influence of mechanical ventilation by positive airway pressure on pulmonary edema and interstitial fluid during the inspiratory phase of the respiratory cycle.

Prediction of posttraumatic adult respiratory distress syndrome by albumin excretion rate eight hours after admission.

Adult respiratory distress syndrome (ARDS) in trauma victims carries a mortality on the order of 50%. An early feature is an increased capillary permeability causing an extravasation of plasma proteins and water, leading to interstitial edema. In the kidney, the increase in microvascular permeability is manifested as increased albumin excretion detectable by sensitive immunoassay. Forty seven trauma victims were studied for 5 days; 32 of them had Injury Severity Scores > 18. A diagnosis of ARDS was made on the recommendations of the American-European Consensus Conference on ARDS (1994). Eight patients developed ARDS, five developed pulmonary dysfunction, and the remainder showed no significant pulmonary abnormality. Using the near patient urine albumin immunoassay, albumin excretion rate (AER) was measured after admission. For patients with Injury Severity Score > 18, the median (95% confidence interval) AER 8 hours after admission was 63 (range, 40-99) microg per minute for those without impaired lung function and 339 (range, 162-454) microg per minute for those in the combined ARDS and pulmonary dysfunction group (Mann-Whitney test, p = 0.0004). The median AER was 51 (range, 27-98) microg per minute for patients with Injury Severity Score < 18. The positive predictive value for the development of ARDS or pulmonary dysfunction of AER > 130 microg per minute was 85%, with a negative predictive value of 95%. These data indicate that the capillary leak associated with the subsequent development of pulmonary dysfunction and ARDS can be detected within 8 hours of admission at the patient's bedside, thus providing a means of early identification of patients at greatest risk and allowing for early intervention.

Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis.

Tissue factor pathway inhibitor (TFPI) is an anticoagulant protein primarily synthesized by the endothelium. A major fraction (approximately 85%) of TFPI remains associated with the endothelium, whereas a small fraction (approximately 15%) is secreted into the blood. In our attempts to search for a marker(s) of endothelial injury in the setting of adult respiratory distress syndrome (ARDS), we retrospectively measured plasma TFPI levels in patients at risk for and with ARDS caused by several etiologic factors. Plasma von Willebrand factor antigen (vWF-Ag), another endothelial-specific protein, was also measured in these patients. The mean plasma TFPI levels were slightly elevated (approximately 1.3-fold), whereas vWF-Ag levels were significantly elevated (approximately 3-fold) in the at-risk group as compared with those in the normal subjects. Both the TFPI (approximately 1.8-fold) and the vWF-Ag (approximately 4-fold) levels were further elevated in the ARDS group. Moreover, the sequential plasma samples from patients with ARDS had progressively increased levels of vWF-Ag and TFPI up to Days 4 and 8, respectively. Neither plasma vWF-Ag nor TFPI levels correlated with mortality in the at-risk group or the ARDS group. TFPI levels were also measured in bronchoalveolar lavage fluids (BALF). The levels (ng/ml) were: normal subjects, 0.05 +/- 0.02 SE; at-risk group, 0.35 +/- 0.16 SE; ARDS group, 0.99 +/- 0.28 SE. Thus, the BALF TFPI levels were increased approximately 7-fold in the at-risk group and approximately 20-fold in the ARDS group relative to the value in the normal subjects. These findings indicate increased local synthesis of TFPI in the alveolar space both in the at-risk patients and in those with ARDS. In additional studies in a primate model of sepsis, lethal doses (LD100) of E. coli administered to baboons resulted in a progressive increase in TFPI levels (approximately 2-fold at 6 h), whereas sublethal doses caused only minimal increase (approximately 1.2-fold). The vWF-Ag levels were elevated approximately 5-fold after infusion of LD100 concentrations of E. coli at 6 h and 4-fold after infusion of sublethal concentrations of E. coli at 24 h. Autopsies on animals in the LD100 group revealed pulmonary congestion, leukocyte infiltration, edema, and hemorrhage, all suggestive of acute lung injury. Thus, in the setting of acute lung injury plasma vWF-Ag appears to be considerably increased prior to significant damage to the endothelium, whereas increased plasma TFPI occurs only after severe injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Cytokine, complement, and endotoxin profiles associated with the development of the adult respiratory distress syndrome after severe injury.

The adult respiratory distress syndrome (ARDS) is a frequent complication after severe accidental trauma. This study examines the hypothesis that increased systemic concentrations of proinflammatory cytokines, endotoxin, or complement fragments may predict the development of ARDS. Prospective, observational study. Two Level I university trauma centers. Fifteen severely injured patients (Injury Severity Score of > or = 25). Standard emergency department, operating room, and intensive care unit management. Plasma samples were obtained at 4-hr intervals from the time of injury and were assayed for concentrations of endotoxin, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and complement fragments C3a and C4a. Hemodynamic and oxygen metabolism variables also were measured at 4-hr intervals after injury. Seven patients developed ARDS and eight patients did not. The PaO2/FIO2 ratio was significantly decreased in the patients with ARDS compared with non-ARDS patients as early as 4 hrs postinjury, and remained significantly decreased throughout the initial 24 hrs after severe accidental injury. Plasma IL-8, IL-6, C3a, and C4a concentrations were markedly increased starting in the immediate postinjury period in both ARDS and non-ARDS patients, but no significant differences were found between the two groups until 16 hrs after injury when plasma IL-8, C3a, and C4a concentrations became significantly higher in the ARDS group. Neither the ARDS nor non-ARDS patients showed the presence of circulating IL-1 beta, TNF-alpha, or endotoxin at any postinjury time point. These results demonstrate that measurements of plasma concentrations of proinflammatory cytokines, endotoxin, or complement fragments are not helpful in predicting the development of ARDS after severe accidental injury.

Urine Hydrogen Peroxide During Adult Respiratory Distress Syndrome in Patients With and Without Sepsis

The lung injury in adult respiratory distress syndrome (ARDS) has been associated with increased expiratory hydrogen peroxide (H2O2) concentrations. Furthermore, patients with sepsis and ARDS are reported to have greater serum scavenging of H2O2 than patients with ARDS only. We hypothesized that the systemic presence of H2O2 would be detectable in the urine of these two groups of patients and that, in the case of ARDS sepsis, the relative contribution of each disease to the production this analyte would be discernible. Accordingly, we used an in vitro radioisotope assay to follow the weekly course of urine H2O2 levels in ARDS patients with and without sepsis, and in samples from control non-ARDS patients with sepsis with indwelling urinary catheters and in samples provided by healthy volunteers. Thirty patients with ARDS were included in the study: 23 had sepsis and 7 were sepsis free. An indwelling catheter was used to collect urine from each patient over a 24-h period, first within 48 h of ICU admission and then every seventh day over the course of their illness. Urine H2O2 was measured by competitive decarboxylation of 1-14C-alpha-ketoglutaric acid by H2O2. Urine samples were provided by 20 healthy volunteers while, in 10 non-ARDS patients with sepsis, urine was collected over one 24-h period following a 5-day minimum with an indwelling urinary catheter. Urine H2O2 concentration in healthy control subjects (88 +/- 4 mumol/L) and non-ARDS patients with urinary catheters (96 +/- 5 mumol/L) was not significantly different. During the first 48 h in the ICU, urine H2O2 in patients with ARDS only (295 +/- 29 mumol/L) was significantly lower (p < 0.05) than patients with ARDS and sepsis (380 +/- 13 mumol/L); however, the lung injury scores of these two groups did not differ. Furthermore, within the first 48 h, the urine H2O2 of the patients with ARDS and sepsis who did not survive (427 +/- 19 mumol/L; n = 7) was significantly higher than that in patients who survived sepsis (352 +/- 14 mumol/L; n = 15). Thereafter, the lung injury scores and urine H2O2 levels of the nonsurvivor ARDS-sepsis group remained significantly higher compared with the other two groups. At lung injury scores of 3 and 2, regardless of days in ICU, the patients with ARDS only had significantly lower urine H2O2 (266 +/- 30 mumol/L and 167 +/- 24 mumol/L, respectively) compared with the survivor ARDS-sepsis group (376 +/- 19 mumol/L and 250 +/- mumol/L). When the patients with ARDS (both ARDS only and with sepsis) recovered, their urine H2O2 concentration did not differ from the control groups (healthy donors and patients without ARDS). Lung injury scores did not differentiate patients with ARDS and sepsis from patients with ARDS only during the first 10 days in the ICU; however, urine H2O2 levels were significantly greater in the patients with ARDS and sepsis. Moreover, despite no initial difference in lung injury, patients who did not survive ARDS and sepsis had consistently greater urine H2O2 concentration than patients who survived sepsis. The urine H2O2 level in the ARDS-only group was about 70 percent of the level in the survivor ARDS and sepsis group, suggesting that ARDS alone is the major contributor to the H2O2 oxidant processes during combined ARDS and sepsis. Furthermore, these studies demonstrate that urine H2O2 may be a useful analyte to differentiate the severity of oxidant processes in patients with ARDS and sepsis albeit the prognosis appears to be survival or nonsurvival.

Effect of Tidal Volume on Gas Exchange and Oxygen Transport in the Adult Respiratory Distress Syndrome

The effect of tidal volume (VT) on gas exchange and oxygen delivery (DO2) was studied in nine patients with adult respiratory distress syndrome (ARDS) and in 10 postoperative open-heart surgery patients (CABG). During controlled mechanical ventilation, VT was initially 10 to 12 ml/kg, followed by an increase and reduction of 25% (1.25 VT and 0.75 VT, respectively). In both groups of patients, dead space (VD) correlated strongly with VT (p < 0.001), while the VD/VT ratio was independent of VT. PaO2 tended to increase in CABG patients and decrease in ARDS patients at 1.25 VT. Arterial oxygen saturation (SaO2) did not change at 1.25 VT but decreased at 0.75 VT (p < 0.001) in the ARDS group. Venous admixture (QS/QT) decreased with 1.25 VT and increased with 0.75 VT (p < 0.001). A relatively larger increase in cardiac output compensated for the increased QS/QT and the reduced SaO2, resulting in significantly higher DO2 with 0.75 VT (p < 0.01). A lower VT resulted in improved balance between pulmonary gas exchange and whole body oxygen supply.

Urinary Desmosine Excretion as a Marker of Lung Injury in the Adult Respiratory Distress Syndrome

Desmosine, the intermolecular and intramolecular cross link between the chains of elastin polypeptide, may be useful as a marker of a lung injury in adult respiratory distress syndrome (ARDS). A radioimmunoassay for rabbit antibody developed against desmosine, conjugated to bovine serum albumin, can detect as little as 100 pg of desmosine in plasma or urine. Desmosine is not metabolically absorbed, reused, or catabolized by the body, but rather eliminated unchanged in the urine as low molecular weight peptides. The lung is relatively rich in elastin, and we reasoned that a timed collection could be used as an index of elastin degradation in vivo. A 2-h collection of urine for desmosine assay was obtained at the time of Swan-Ganz catheter insertion in 41 consecutive patients. On the basis of clinical and initial Swan-Ganz catheter data, the patients were assigned to one of three groups: an ARDS group (n = 12); a cardiogenic pulmonary edema (CPE) group (n = 12); and a critically ill, nonpulmonary edema group (NPE, n = 17). The mean urine desmosine concentration (mg/L) for the ARDS group (0.728 +/- 0.22 SE) differed from the CPE group (0.149 +/- 0.07; p less than 0.001). The total excretion (microgram/2 h) was 64.95 +/- 24.7 in the ARDS group and 24.71 +/- 11.7 in the CPE group (p less than 0.05). Urine desmosine concentration/serum creatinine index for the ARDS group (0.78 +/- 0.28) was greater than in the CPE group (0.07 +/- 0.04; p = 0.019). Desmosine excretion was increased in the NPE group compared with CPE and ARDS groups, possibly reflecting heterogeneity in this group. In the differentiation of ARDS from CPE, we conclude that substantial increases in urinary desmosine excretion favor a diagnosis of ARDS.

Components of excess ventilation in patients initiated on mechanical ventilation

To determine the causes of excess minute ventilation in patients initiated on mechanical ventilation. Prospective study of recently intubated, mechanically ventilated patients. The medical ICU in a county hospital. Fifty-two mechanically ventilated medical ICU patients were studied within 36 hrs of intubation. Patients were all supported with volume-cycled ventilation in the assist-control mode. Timed expired gas collection and an arterial blood gas. Measurements of minute ventilation and CO2 production (VCO2) were made from a timed expired gas collection. PaCO2 was sampled during the gas collection and deadspace was determined. Minute ventilation, VCO2, deadspace, and PaCO2 values in the patients were compared with predicted normal values, and excess minute ventilation due specifically to each component was calculated. Patients were separated clinically into groups: adult respiratory distress syndrome (ARDS), sepsis, obstructive lung disease, pneumonia, and drug overdose. Comparisons were then made between groups. Excess minute ventilation for the entire study population was secondary to increased deadspace (39%), low PaCO2 (36%), increased VCO2 (15%), and the interactive effect of deadspace and VCO2 (10%). VCO2 contributed little to excess minute ventilation early in respiratory failure, even in the ARDS and sepsis groups. Deadspace contributed significantly to excess minute ventilation in all groups, especially in the ARDS group, where it accounted for 53% of the excess ventilation. Low PaCO2 set-point was the predominant cause of excess minute ventilation in the sepsis group, where it contributed to 57% of their total excess minute ventilation. Although all groups initiated on mechanical ventilation had an excess ventilatory requirement, the contribution of individual components varied considerably between clinical groups.

The Effects of Positive End-expiratory Pressure on Respiratory Resistance in Patients with the Adult Respiratory Distress Syndrome and in Normal Anesthetized Subjects

We investigated the effects of positive end-expiratory pressure (PEEP) upon respiratory resistance during mechanical ventilation in 21 subjects anesthetized for surgery (normal subjects) and in 11 patients with the adult respiratory distress syndrome (ARDS). We measured tracheal pressure (Ptr) near the end of the endotracheal tube through a 1.5-mm ID catheter and airflow (V) at 0, 5, and 10 cm H2O PEEP (normal subjects) and at 0, 5, 10, 15, and 20 cm H2O PEEP (patients with ARDS). We computed respiratory system static elastance (Estrs), maximal (Rrsmax) and minimal (Rrsmin) inspiratory resistance by the end-inspiratory occlusion method during constant-flow inflation. Rrsmin represents the ohmic respiratory resistance, whereas Rrsmax is Rrsmin plus the additional respiratory impedance caused by the stress adaptation phenomena of the respiratory system tissues and to time constant inhomogeneities between lung units (pendelluft). The difference (Rrsmax - Rrsmin) has been termed DRrs. We also computed expiratory resistance (Rrsexp) at preselected volume (50% of expiration; Rrsexp50) and flow (0.3 L/s; Rrsexp0.3) using the equation: Rrsexp = (Pelrs(t) - Ptr(t]/Flow(t), where elastic recoil pressure (Pelrs) at time t was computed as:Estrs . V(t) + PEEP, in which V(t) is the volume above end-expiratory volume at time t. We found that (1) at PEEP 0, expiratory resistances (Rrsexp50: 7.38 +/- 1.92 versus 5.35 +/- 1.97 cm H2O.L-1.s) and DRrs (3.08 +/- 1.9 versus 1.66 +/- 0.77 cm H2O.L-1.s) were significantly higher in the ARDS group than in the normal group.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen delivery-dependent oxygen consumption in acute respiratory failure

To investigate whether oxygen consumption (VO2) is dependent on oxygen delivery (DO2) in adult respiratory distress syndrome (ARDS) and non-ARDS acute respiratory failure. Intervention study of a consecutive sample of patients admitted to the ICU with the diagnosis of acute respiratory failure. Tertiary care center. Thirteen consecutive patients with a diagnosis of ARDS and 11 with a diagnosis of respiratory failure not due to ARDS. Patients were monitored with an oximetric pulmonary artery catheter and mechanically ventilated. DO2 was decreased by the application of positive end-expiratory pressure (PEEP) (20 cm H2O), and subsequently increased by an iv infusion of dobutamine (10 micrograms/kg.min). After the application of PEEP, DO2 decreased significantly in both groups. However, VO2 decreased significantly (p less than .01) only in the ARDS group. When dobutamine was infused, DO2 increased significantly (p less than .01) in both groups, but VO2 increased only in ARDS patients. DO2 correlated significantly with VO2 both in ARDS (r2 = .81, p less than .01) and in non-ARDS (r2 = .38, p less than .05) patients. The correlation coefficient was significantly higher for ARDS than for non-ARDS patients. Comparing the slopes of the regression lines, a stronger dependency of VO2 on DO2 was found in ARDS than in non-ARDS respiratory failure (p less than .001). The oxygen extraction ratio correlated with DO2 in non-ARDS patients (r2 = .49, p less than .05), but not in ARDS patients. VO2 is dependent on DO2 over a wide range of DO2 values in acute respiratory failure. This dependency phenomenon is much stronger in ARDS than in respiratory failure due to other causes. Due to the abnormal dependency of VO2 on DO2, changes in the oxygenation status may not be reflected by changes in mixed venous oxygen saturation in ARDS.

Gamma scintigraphic imaging of lung microvascular permeability in adult respiratory distress syndrome

The sequence of lung microvascular permeability (LMVP) changes in early direct posttraumatic and late indirect pancreatitis-induced adult respiratory distress syndrome (ARDS) was studied and compared with that of a control group, as well as non-ARDS ICU patients. A computerized large field of view gamma camera was used to measure LMVP simultaneously over both lungs by In 113m-labeled transferrin and Tc 99m-labeled erythrocytes. The LMVP index (LMVPI) (%/h) was used to quantify LMVP in the dynamic scintigraphic measurement. In the control group the LMVPI was 2.6 +/- 2.8%/h for the right and 2.0 +/- 2.8%/h for the left lung. Similar values were found in mechanically ventilated ICU patients without ARDS (group A) on admission (right LMVPI 3.2 +/- 2.6, left LMVPI 2.6 +/- 2.7%/h) and 4 days later (right LMVPI 3.9 +/- 2.6, left LMVPI 2.3 +/- 1.8%/h). Interestingly, the initial evaluation of patients with direct early posttraumatic ARDS (lung contusion) (group B) showed significantly (p less than .01) elevated LMVP for the contused side (LMVPI 10.8 +/- 5.1%/h), but normal values for the nontraumatized lung (LMVPI 3.9 +/- 3.4%/h), whereas 4 days later the LMVP increased significantly (p less than .05) on the primarily healthy side (LMVPI 8.0 +/- 5.0%/h) while remaining elevated for the traumatized lung (LMVPI 10.9 +/- 6.0%/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoreactive interleukin-1 in bronchoalveolar lavage fluid of high-risk patients and patients with the adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is characterized by increased neutrophils and macrophages in bronchoalveolar lavage (BAL) fluid. Interleukin-1 (IL-1), an inflammatory mediator produced by macrophages, has been shown to be chemotactic for neutrophils and to stimulate lymphocyte activation and proliferation of fibroblasts. BAL was performed in patients with ARDS, patients at high risk to develop ARDS, and in normal nonsmokers. After removal of cells and surfactant-complexed lipids by centrifugation, the remaining supernatant was concentrated by ultrafiltration utilizing membranes retaining substances greater than 5000 daltons. The concentrate was assayed for immunoreactive IL-1 beta by a radioimmunoassay method. Patients with ARDS (n = 9) had an IL-1 level of 184 +/- 67 pg/ml, high-risk patients (n = 9) had 172 +/- 62 pg/ml, and normals (n = 10) had 4 +/- 1 pg/ml. There was a significant (p less than or equal to .05) increase in IL-1 in the ARDS and risk groups compared to normals. IL-1 was detected in serum from patients with ARDS (n = 19), high risk (n = 19), and normals (n = 8), but no difference was noted among the three groups. BAL cell differentials revealed that neutrophils were increased (p less than .05) in both the ARDS (59 +/- 10%) and high-risk (65 +/- 8%) groups compared to normals (2 +/- 1%). There was a correlation (r = 0.64, p less than .001) between IL-1 levels and BAL protein concentration. BAL IL-1 levels were highest in patients with the fully developed syndrome but were also elevated in patients at high risk. The absence of significant amounts of IL-1 in serum suggests that it may be produced within the lung.

Pulmonary vascular permeability during the adult respiratory distress syndrome: a positron emission tomographic study.

The natural history of change in pulmonary vascular permeability (PVP) during the adult respiratory distress syndrome (ARDS) is unknown. Therefore, we evaluated PVP by measuring the pulmonary transcapillary escape rate (PTCER) for transferrin with positron emission tomography (PET) in 15 ARDS patients, including 5 patients studied within 4 days of onset and 13 patients studied at least 7 days after onset. In 3 patients, studies were performed at both early and late stages. These results were compared to 12 non-smoking adult volunteers. Regional PTCER and extravascular lung density (EVD) were determined from a 1-h PET scan after intravenous injection of gallium-68 citrate, which binds rapidly to native transferrin. Oxygenation, radiologic score, as well as outcome were recorded for each patient. Mean PTCER was highest during the early phase of ARDS (560 +/- 275 x 10(-4) min-1) although PTCER in the late ARDS patients was also significantly higher than in normals (319 +/- 187 vs 58 +/- 33 x 10(-4) min-1; p less than .01). EVD was similar in both early and late ARDS groups (.39 +/- .08 and .37 +/- .13 g/ml lung, respectively) and markedly higher than in normals (.22 +/- .05 g/ml lung, p less than 0.01). PTCER decreased in each of the 3 serial studies. The correlation between PTCER and EVD was poor, as were correlations for either PTCER or EVD versus changes in oxygenation, radiologic score, survival, or duration of ventilator dependency. In the late ARDS patients, PTCER was usually elevated even if EVD had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Causes of mortality in patients with the adult respiratory distress syndrome: Montgomery AB, Stager MA, Carrico CJ, et al. Am Rev Respir Dis 132:485, 1985

This study analyzed the factors causing and contributing to death in patients with the adult respiratory distress syndrome (ARDS). Two hundred seven patients were prospectively identified as being at risk for development of ARDS. Forty-seven patients developed ARDS, and the remaining 160 patients were used as a comparison control group. The severity of dysfunction in 8 organ systems and the presence of sepsis syndrome were determined by chart review after discharge or death. Sepsis syndrome was specifically defined by signs and laboratory tests reflecting infection or inflammation plus evidence of a deleterious systemic effect (hypotension, reduced systemic vascular resistance, or unexplained metabolic acidosis). Mortality was 68% in the ARDS group compared to 34% in the control group (p < 0.005). Only 16% (5 of 32) of deaths in the ARDS group were from irreversible respiratory failure. Most deaths in the first 3 days after entry into the study could be attributed to the underlying illness or injury. The ...

Angiotensin Converting Enzyme in Bronchoalveolar Lavage in ARDS

Angiotensin converting enzyme (ACE) is present in the endothelial cells of the normal lung where it converts angiotensin I to angiotensin II and inactivates bradykinin. It has been suggested that during endothelial injury ACE is sloughed into the blood, and that if the alveolar capillary membrane is injured, also into the alveolar lining fluid. Seven patients with adult respiratory distress syndrome (ARDS), were compared to 11 normal control subjects, nine patients with sarcoidosis, and six with idiopathic pulmonary fibrosis. Total, differential cell counts and ACE determinations were performed on bronchoalveolar lavage fluid in the ARDS group. ACE was detectable in the BAL of all but one ARDS patient. It was concluded that BAL ACE is elevated in some ARDS patients, especially those with infectious causes of lung injury. Increased ACE may reflect endothelial damage or local increase in ACE production in response to sepsis.

Causes of Mortality in Patients with the Adult Respiratory Distress Syndrome

This study analyzed the factors causing and contributing to death in patients with the adult respiratory distress syndrome (ARDS). Two hundred seven patients were prospectively identified as being at risk for development of ARDS. Forty-seven patients developed ARDS, and the remaining 160 patients were used as a comparison control group. The severity of dysfunction in 8 organ systems and the presence of sepsis syndrome were determined by chart review after discharge or death. Sepsis syndrome was specifically defined by signs and laboratory tests reflecting infection or inflammation plus evidence of a deleterious systemic effect (hypotension, reduced systemic vascular resistance, or unexplained metabolic acidosis). Mortality was 68% in the ARDS group compared to 34% in the control group (p less than 0.005). Only 16% (5 of 32) of deaths in the ARDS group were from irreversible respiratory failure. Most deaths in the first 3 days after entry into the study could be attributed to the underlying illness or injury. The majority of late deaths were related to sepsis syndrome. Of the 22 patients with ARDS who died after 3 days, 16 (73%) met our criteria for sepsis syndrome. There was a sixfold increase in sepsis syndrome after ARDS compared with that in the control group (p less than 0.001). When sepsis syndrome preceded the ARDS, the abdomen was the predominant source, but when sepsis syndrome occurred after the onset of ARDS there was usually a pulmonary source. Our findings indicate that sepsis syndrome, rather than respiratory failure, is the leading cause of death in patients with ARDS.

Static pressure-volume curves and effect of positive end-expiratory pressure on gas exchange in adult respiratory distress syndrome

Fifteen patients with adult respiratory distress syndrome (ARDS) were studied: 11 in the early stage of ARDS (group 1); 4 in the late stage (group 2). The inspiratory and expiratory static pressure-volume (P-V) curves of the respiratory system were compared to the pulmonary shunt (Qsp/Qt) when PEEP was increased; cardiac output was kept constant. In group 1 patients, we found that a concavity on the P-V curves was associated with an abrupt decrease in Qsp/Qt when PEEP was increased; the concavity on the expiratory curve was correlated with the change in Qsp/Qt but not the concavity on the inspiratory curve. In group 2 patients, the P-V curves were found rectilinear and Qsp/Qt was not abruptly decreased when PEEP was increased. Expiratory P-V curve can be used to determine: first, whether a patient should be ventilated with PEEP; second, the PEEP level which can be set on the respirator. In group 1 patients, when PEEP was set to a value corresponding to the inflexion point, i.e., the point of departure from the exponential shape (mean value 14.6 +/- 2.8 cm H2O), Qsp/Qt compared to zero PEEP was abruptly decreased to 87.6 +/- 6%; further increase in PEEP had little advantage.