Fluid intake-related association between urine output and mortality in acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS), a complex response to various insults, has a high mortality rate. As pulmonary edema resulting from increased vascular permeability is a hallmark of ARDS, management of the fluid status, including the urine output (UO) and fluid intake (FI), is essential. However, the relationships between UO, FI, and mortality in ARDS remain unclear. This retrospective study aimed to investigate the interactive associations among UO, FI, and mortality in ARDS. METHODS: This was a secondary analysis of a prospective randomized controlled trial performed at 10 centers within the ARDS Network of the National Heart, Lung, and Blood Institute research network. The total UO and FI volumes within the 24-h period preceding the trial, the UO to FI ratio (UO/FI), demographic data, biochemical measurements, and other variables from 835 patients with ARDS, 539 survivors, and 296 non-survivors, were analyzed. The associations among UO, FI, the UO/FI, and mortality were assessed using a multivariable logistic regression. RESULTS: In all 835 patients, an increased UO was significantly associated with decreased mortality when used as a continuous variable (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.98-0.99, P = 0.002) and as a quartile variable (OR of Q2 to Q4: 0.69-0.46, with Q1 as reference). To explore the interaction between UO and FI, the UO/FI was calculated, and a cut-off value of 0.5 was detected for the association with mortality. For patients with a UO/FI ≤0.5, an increased UO/FI was significantly associated with decreased mortality (OR: 0.09, 95% CI: 0.03-0.253, P <  0.001); this association was not significant for patients with UO/FI ratios > 0.5 (OR: 1.04, 95% CI: 0.96-1.14, P = 0.281). A significant interaction was observed between UO and the UO/FI. The association between UO and mortality was significant in the subgroup with a UO/FI ≤0.5 (OR: 0.97, 95% CI: 0.96-0.99, P = 0.006), but not in the subgroup with a UO/FI > 0.5. CONCLUSIONS: The association between UO and mortality was mediated by the UO/FI status, as only patients with low UO/FI ratios benefitted from a higher UO.

Return to work and lost earnings after acute respiratory distress syndrome: a 5-year prospective, longitudinal study of long-term survivors.

BACKGROUND: Delayed return to work is common after acute respiratory distress syndrome (ARDS), but has undergone little detailed evaluation. We examined factors associated with the timing of return to work after ARDS, along with lost earnings and shifts in healthcare coverage. METHODS: Five-year, multisite prospective, longitudinal cohort study of 138 2-year ARDS survivors hospitalised between 2004 and 2007. Employment and healthcare coverage were collected via structured interview. Predictors of time to return to work were evaluated using Fine and Grey regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data. RESULTS: Sixty-seven (49%) of the 138 2-year survivors were employed prior to ARDS. Among 64 5-year survivors, 20 (31%) never returned to work across 5-year follow-up. Predictors of delayed return to work (HR (95% CI)) included baseline Charlson Comorbidity Index (0.77 (0.59 to 0.99) per point; p=0.04), mechanical ventilation duration (0.67 (0.55 to 0.82) per day up to 5 days; p<0.001) and discharge to a healthcare facility (0.49 (0.26 to 0.93); p=0.03). Forty-nine of 64 (77%) 5-year survivors incurred lost earnings, with average (SD) losses ranging from US$38 354 (21,533) to US$43 510 (25,753) per person per year. Jobless, non-retired survivors experienced a 33% decrease in private health insurance and concomitant 37% rise in government-funded coverage. CONCLUSIONS: Across 5-year follow-up, nearly one-third of previously employed ARDS survivors never returned to work. Delayed return to work was associated with patient-related and intensive care unit/hospital-related factors, substantial lost earnings and a marked rise in government-funded healthcare coverage. These important consequences emphasise the need to design and evaluate vocation-based interventions to assist ARDS survivors return to work.

Prognosis of patients with acute respiratory distress syndrome on extracorporeal membrane oxygenation: the impact of urine output on mortality.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been utilized for patients in critical condition, including life-threatening respiratory failure and postcardiotomy cardiogenic shock. This study analyzed the outcomes of patients with acute respiratory distress syndrome (ARDS) treated by ECMO and identified the relationship between prognosis and urine output (UO) obtained on the first day of ECMO support. METHODS: This study reviewed the medical records of 81 ARDS patients after ECMO support on a specialized cardiovascular surgery intensive care unit of a tertiary care university hospital between May 2006 and December 2011. Demographic, clinical, and laboratory variables were retrospectively collected as survival predictors. RESULTS: The overall mortality rate was 55.5%. A multiple logistic regression analysis indicated that the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, mean arterial pressure, platelet count, and UO on day 1 of ECMO support were independent risk factors for hospital mortality. By using the areas under the receiver operating characteristic (AUROC) curve, UO obtained on the first day of ECMO support demonstrated good discriminative power (AUROC 0.754 ± 0.056, p < 0.001). Urine output had the best discriminative power, the best Youden index, and the highest overall correctness of prediction. Cumulative survival rates at the 6-month follow-up differed significantly (p < 0.001) for UO 1,432 mL or greater on day 1 of ECMO support versus those with UO less than 1,432 mL on day 1 of ECMO support. CONCLUSIONS: In ARDS patients receiving ECMO support, UO obtained on the first day of ECMO support showed good prognostic ability in predicting hospital mortality.

Effects of airway pressure release ventilation on blood pressure and urine output in children.

OBJECTIVE: Increased intrathoracic pressures during airway pressure release ventilation (APRV) may compromise systemic venous return resulting in decreased cardiac output and renal perfusion. We sought to study the short-term effect of APRV on blood pressure (BP) and urine output (UO) in children with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). DESIGN: Retrospective cohort study. PATIENTS: All patients with ALI/ARDS who were admitted to our Pediatric Intensive Care Unit (PICU) between 1/00 and 06/04, and who were ventilated with APRV (for at least 12 hr) for worsening oxygenation while on conventional ventilation (CV). MEASUREMENTS AND RESULTS: Medical records were reviewed for patients' demographics, Pediatric Risk of Mortality (PRISM III) score, admitting diagnosis, ventilator settings, gas exchange data, heart rate (HR), central venous pressure (CVP), blood pressure (BP), UO, and use of other therapies [sedatives, pressors, inotropes, and intravenous fluid (IVF)]. Eleven patients met our inclusion and exclusion criteria with a mean age of 6.2 +/- 4.8 years (range: 1-15 years), a weight of 35.5 +/- 29.5 kg (range: 12-90 kg), and a PRISM score of 18.4 +/- 9.6 (range: 2-36). Within 10 hrs of APRV, patients' mean airway pressure (Paw) increased from 16.1 +/- 6.6 to 21.1 +/- 5.5 cm of H(2)O (P = 0.04). Despite a higher Paw there were no differences in HR, CVP, BP, UO, IVF and use of other therapies while on CV or APRV (P > 0.10). CONCLUSION: In children with ALI/ARDS, despite a higher Paw, APRV does not affect BP or UO.

Higher urine nitric oxide is associated with improved outcomes in patients with acute lung injury.

RATIONALE: Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI). OBJECTIVES: We tested two hypotheses in patients with ALI: (1) higher levels of urine NO would be associated with worse clinical outcomes, and (2) ventilation with lower VT would reduce urine NO as a result of less stretch injury. METHODS: Urine NO levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg VT ventilation. The data were expressed corrected and uncorrected for urine creatinine (Cr). RESULTS: Higher baseline levels of urine NO to Cr were associated with lower mortality (odds ratio, 0.43 per log(10) increase in the ratio), more ventilator-free days (mean increase, 1.9 d), and more organ-failure-free days (mean increase, 2.3 d) on multivariate analysis (p < 0.05 for all analyses). Similar results were obtained using urine NO alone. NO to Cr levels were higher on Day 3 in the 6 ml/kg than in the 12 ml/kg VT group (p = 0.04). CONCLUSIONS: Contrary to our hypothesis, higher urine NO was associated with improved outcomes in ALI at baseline and after treatment with the 6 ml/kg VT strategy. Higher endogenous NO may reflect less severe lung injury and better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with ALI.

Early isovolaemic haemofiltration in oliguric patients with septic shock.

OBJECTIVE: To evaluate the effects of early short-term, isovolaemic haemofiltration at 45 ml/kg/h on physiological and clinical outcomes in patients with septic shock. DESIGN: Retrospective study before and after a change of unit protocol (study period 8 years). SETTING: Intensive care unit of metropolitan hospital. PATIENTS: Eighty patients with septic shock. INTERVENTIONS: Introduction of a new septic shock protocol based on early isovolaemic haemofiltration (EIHF). In the pre-EIHF period (before), 40 patients received conventional supportive therapy. In the post-EIHF period (after), 40 patients received EIHF at 45 ml/kg/h of plasma-water exchange over 6 h followed by conventional continuous venovenous haemofiltration (CVVH). Anticoagulation policy remained unchanged. MEASUREMENTS AND MAIN RESULTS: The two groups were comparable for age, gender and baseline APACHE II score. Delivered haemofiltration dose was above 85% of prescription in all patients. PaO2/FiO2 ratio increased from 117+/-59 to 240+/-50 in EIHF, while it changed from 125+/-55 to 160+/-50 in the control group (p<0.05). In EIHF patients, mean arterial pressure increased (95+/-10 vs 60+/-12 mmHg; p<0.05), and norepinephrine dose decreased (0.20+/-2 vs 0.02+/-0.2 microg/kg/min; p<0.05). Among EIHF patients, 28 (70%) were successfully weaned from the ventilator compared with 15 (37%) in the control group (p<0.01). Similarly, 28-day survival was 55% compared with 27.5% (p<0.05). Length of stay in the ICU was 9+/-5 days compared with 16+/-4 days (p<0.002). CONCLUSIONS: In patients with septic shock, EIHF was associated with improved gas exchange, haemodynamics, greater likelihood of successful weaning and greater 28-day survival compared with conventional therapy.

Early post-traumatic acute respiratory distress syndrome and albumin excretion rate: a prospective evaluation of a 'point-of care' predictive test.

All patients sustaining major trauma exhibit increased capillary permeability, manifested as micro-albuminuria. Urinary albumin excretion rate (AER) measured on intensive care units (ICU) can predict early post-traumatic acute respiratory distress syndrome (ARDS). This prospective study sought to evaluate AER as a practical predictive test for early ARDS. Staff at the participating centres were trained in the use of the Behring Turbitimer and the concept of AER as a predictor of early post-traumatic ARDS. AER was measured every 2 h for the first 24 h, on 54 adult blunt trauma admissions (ISS>/=18). A diagnosis of early acute lung injury (ALI) or ARDS was made using the American-European Consensus Conference criteria. Eleven patients developed ARDS, ten developed ALI, and 23 had no pulmonary dysfunction. The AER was significantly greater in those who developed ARDS 8 and 18 h after admission. The positive predictive value of the test was 64% at 8 h, the negative predictive power 73%. The test was performed most consistently in the middle 10 h of the study period. If intervention had been based on the 8 h data point result, 75% patients who had the test performed and later developed ARDS would have had intervention appropriately. In principle, testing for AER as a predictor of post-traumatic ARDS on ICU is feasible, however, this study has underlined the challenges of introducing new concepts into the ICU environment.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Simplified method for measuring urinary leukotriene E4.

The conventional method for measuring urinary leukotriene E4 (LTE4) is by reversed-phase high-performance liquid chromatography (RP-HPLC), followed by radioimmunoassay (RIA) or enzyme immunoassay (EIA). We measured urinary LTE4 levels by two methods, HPLC with EIA and EIA alone after initial crude extraction of urine using an octadecyl reversed-phase extraction cartridge (Sep-Pak). Ninety-three urine samples from normal subjects and patients with bronchial asthma and adult respiratory distress syndrome were tested. The results showed that urinary LTE4 levels measured by EIA significantly correlated with those measured by HPLC plus EIA in the three groups (r = 0.88, 0.85, 0.68). The absolute values of urinary LTE4 measured by EIA without HPLC purification were higher than by EIA with HPLC purification. This suggests that HPLC may not be necessary for routine urinary LTE4 quantitation in different clinical situations.

Urinary excretion of polyamines in the adult respiratory distress syndrome.

Polyamines are low molecular weight polycations that are critically important in cellular proliferation and differentiation. To investigate their potential role in acute lung injury, the polyamines spermidine, spermine, and putrescine were measured in 24-h urine collections from intubated patients with ARDS (n = 12) or congestive heart failure with cardiogenic pulmonary edema (CHF, n = 10) and in normal subjects (n = 10). Mean concentrations of putrescine were similar between groups, but spermidine concentrations in patients with ARDS (52.7 +/- 19.7 nmol/mg creatinine) were significantly higher than in normal subjects (4.9 +/- 0.7 nmol/mg), p < .05. Mean concentrations of spermine in ARDS (270.6 +/- 78.1 nmol/mg) were higher than in CHF (1.0 +/- 0.5 nmol/mg), p < .05, and normal subjects (0.3 +/- 0.1 nmol/mg), p < .05. Concentrations of putrescine increased significantly during the first 7 days of ARDS (241.5 +/- 127.1% above baseline, n = 6), p < .05. Urinary polyamine excretion did not correlate with severity of gas exchange or death. These results are the first to suggest a potential role for polyamines in the pathophysiology of ARDS.

Urine hydrogen peroxide during adult respiratory distress syndrome in patients with and without sepsis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Persistent generation of peptido leukotrienes in patients with the adult respiratory distress syndrome.

The time course of leukotriene generation in the adult respiratory distress syndrome (ARDS) was investigated by measurement of urinary leukotriene E4 (LTE4) excretion, the major urinary LT metabolite in humans. Sequential measurements were made in nine subjects entered into the study within 48 h of the onset of ARDS, defined by an arterial/alveolar PO2 ratio of less than 0.3 and radiographic evidence of diffuse bilateral pulmonary edema. Initial urinary LTE4 excretion was significantly elevated (1.250 +/- 0.050 ng/mg creatinine sulphate; n = 7) compared with a non-ARDS postoperative group (0.254 +/- 0.114 ng/mg; n = 5) and normal control subjects (0.035 +/- 0.010 ng/mg; n = 12). LTE4 excretion in the first 24 h was estimated to be 6.9 micrograms, representing a release of 0.1 micrograms/kg/h of peptido leukotrienes into the bloodstream. These values were physiologically important based on a comparison with the increased urinary LTE4 excretion observed after antigen-induced bronchoconstriction in allergic asthmatics (baseline LTE4, 0.06 +/- 0.04 ng/mg; postantigen, 0.56 +/- 0.14 ng/mg; 0.17 micrograms LTE4/24 h; n = 8). In subjects with ARDS, this pathologic LTE4 excretion persisted during a subsequent 5-day study period. Leukotriene E4 excretion was associated with persistent abnormalities in gas exchange, pulmonary edema, and lung compliance, suggesting an important role for peptido leukotrienes in the pathophysiology of ARDS.

Elevated urinary leukotriene E4 excretion in patients with ARDS and severe burns.

Increased synthesis of peptidoleukotrienes may occur in a variety of inflammatory diseases. To test this theory, hospitalized patients with a variety of diseases were studied and urine LTE4 quantitated as an index of total body peptidoleukotriene synthesis. 10 patients with ARDS, 7 of which had additional organ involvement, and 5 patients suffering from severe burn injuries were studied. Patients with uncomplicated ARDS excreted approximately 6-fold higher amounts of LTE4 in urine compared to healthy subjects. When ARDS was complicated by multiple organ failure (MOF), urine LTE4 levels were 2- to 150-fold higher than in healthy volunteers. Patients with severe burn injuries had peak urine LTE4 levels which were approximately 20-fold higher than in healthy volunteers. As additional controls, patients with cardiac arrhythmias (absence of inflammatory disease) and patients with uncomplicated pneumonia (localized inflammation) showed normal or mildly elevated urinary LTE4 levels. The urinary LTE4 levels in ARDS patients did not correlate with serum creatinine, bilirubin, or LDH levels, or with the WBC, nor did renal or liver failure by itself predict extremely elevated urinary LTE4 levels. In conclusion, patients with ARDS or ARDS/MOF and patients with severe injuries and sepsis syndrome excrete higher levels of urinary LTE4 than patients healthy volunteers or patients with limited inflammatory disease. In certain situations, urinary LTE4 levels may be useful as a marker of the degree of inflammation.

Enhanced urinary excretion of leukotriene E4 by patients with multiple trauma with or without adult respiratory distress syndrome.

1. The aim of the present study was to evaluate the systemic synthesis of cysteinyl leukotrienes in patients with multiple trauma. In order to do this, the urinary excretion of leukotriene E4 was assessed in the first 10 days after trauma. 2. Leukotriene E4 was unequivocally identified by g.c.-m.s. in the urine of healthy subjects and patients with multiple trauma after its conversion to 5-hydroxyeicosanoic acid. Leukotriene E4 was routinely isolated from 24 h urine samples by solid-phase extraction followed by reverse-phase h.p.l.c. and was subsequently quantified by r.i.a. 3. Healthy subjects excreted daily 10 +/- 3 nmol of leukotriene E4/mol of creatinine (mean +/- SEM, n = 16) into urine. 4. Patients with multiple trauma who did not develop adult respiratory distress syndrome (n = 7) excreted 76.8 +/- 6.7 nmol of leukotriene E4/mol of creatinine (mean +/- SEM) daily during the first 10 days after trauma, which was significantly (P less than 0.01) more than did healthy subjects. 5. Excretion of leukotriene E4 was even more enhanced in three patients with multiple trauma who developed adult respiratory distress syndrome. Maximal amounts of 593 +/- 185 nmol of leukotriene E4/mol of creatinine (mean +/- SEM) were excreted on day 9 after trauma by these three patients, which corresponds to a 7.7- and a 59-fold increase in excretion of leukotriene E4 compared with patients with multiple trauma who did not develop adult respiratory distress syndrome and healthy subjects, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of peptidoleukotrienes in biological fluids.

Samples of human bronchoalveolar lavage fluid (BALF) and urine were utilized to demonstrate methods for quantitation and validation of leukotrienes (LTs). These methods utilize an enzyme immunoassay (EIA) that uses commercially available reagents, the antibody recognizing LTC4, LTD4, LTE4, and N-acetyl LTE4. BALF containing epithelial lining fluid was collected from atopic asthmatics both before and 5 min after the subjects had been challenged with a local instillation of allergen into the airways. BALF samples collected without allergen challenge had low levels of immunoreactive LTs, whereas samples collected after allergen were markedly elevated. After high-performance liquid chromatography (HPLC) separation of LTs, EIA revealed the presence of LTC4. The identity was validated by incubating LTC4 with a bovine gamma-glutamyl transpeptidase with dipeptidase activity that converted added [3H]-LTC4 as well as LTC4 immunoreactivity to LTE4. Urine samples collected from six healthy volunteers, one patient with adult respiratory distress syndrome (ARDS), and three patients in status asthmaticus were also analyzed for LTs. After HPLC separation of LTs and quantitation by EIA, urine samples from healthy subjects were found to have low but measurable LTE4. In contrast, the urine samples from the patients in status asthmaticus and from the ARDS patient had large elevations of LTE4 levels compared with healthy subjects. When the HPLC fractions containing [3H]LTE4 and LT immunoreactivity in the ARDS sample were treated with acetic anhydride, HPLC analysis indicated that both radiolabel and immunoreactivity now eluted at the retention time of N-acetyl LTE4, the derivatized product of LTE4. The methods described are relatively easy and can be used to measure and validate the existence of peptidoleukotrienes in biological samples.

Adult respiratory distress syndrome as a specific manifestation of a general permeability defect in trauma patients.

To establish whether a general dysfunction, i.e., an increase in permeability, had occurred in 16 trauma patients (6 with adult respiratory distress syndrome [ARDS]), we measured beta 2-microglobulin (beta 2MG), myoglobin (MG), immunoglobulin G (IgG), and transferrin (TF) concentrations in bronchoalveolar lavage fluid (BAL), serum, and urine as well as extravascular lung water content (EVLW) over a period of 14 days. Our results show a positive correlation (p = 0.03) between increases of EVLW, reflecting lung edema, and beta 2MG concentrations in urine of all patients with ARDS, indicating systemically increased permeability. Generalized increase of permeability can also explain the elevation of MG urine concentrations (p = 0.03) together with an EVLW increase, and an increase of BAL protein concentrations (IgG, TF, p less than 0.01) in the early post-trauma phase during the first 48 h after admission. In contrast, commonly used kidney function tests remained unchanged over the time course of 14 days.