URINE HYDROGEN-PEROXIDE DURING ADULT-RESPIRATORY-DISTRESS-SYNDROME INPATIENTS WITH AND WITHOUT SEPSIS

Background: The lung injury in adult respiratory distress syndrome (AR DS) has been associated with increased expiratory hydrogen peroxide (H 2O2) concentrations. Furthermore, patients with sepsis and ARDS are re ported to have greater serum scavenging of H2O2, than patients with AR DS only. We hypothesized that the systemic presence of H2O2 would be d etectable in the urine of these two groups of patients and that, in th e case of ARDS sepsis, the relative contribution of each disease to th e production this analyte would be discernible. Accordingly, we used a n in vitro radioisotope assay to follow the weekly course of urine H2O 2 levels in ARDS patients with and without sepsis, and in samples from control non-ARDS patients with sepsis with indwelling urinary cathete rs and in samples provided by healthy volunteers. Methods: Thirty pati ents with ARDS were included in the study: 23 had sepsis and 7 were se psis 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 the n every seventh day over the course of their illness. Urine H2O2 was m easured by competitive decarboxylation of 1-C-14-alpha-ketoglutaric ac id 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 cathete r. Results: Urine H2O2 concentration in healthy control subjects (88 /- 4 mu mol/L) and non-ARDS patients with urinary catheters (96 +/- 5 mu mol/L) was not significantly different. During the first 48 h in th e ICU, urine H2O2 in patients with ARDS only (295 +/- 29 mu mol/L) was significantly lower (p < 0.05) than patients with ARDS and sepsis (38 0 +/- 13 mu mol/L); however, the lung injury scores of these two group s did not differ. Furthermore, within the first 48 h, the urine H2O2 o f the patients with ARDS and sepsis who did not survive (427 +/- 19 mu mol/L; n = 7) was significantly higher than that in patients who surv ived sepsis (352 +/- 14 mu mol/L; n = 15). Thereafter, the lung injury scores and urine H2O2 levels of the nonsurvivor ARDS-sepsis group rem ained significantly higher compared with the other two groups. At lung injury scores of 3 and 2, regardless of days in ICU, the patients wit h ARDS only had significantly lower urine H2O2 (266 +/- 30 mu mol/L an d 167 +/- 24 mu mol/L, respectively) compared with the survivor ARDS-s epsis group (376 +/- 19 mu mol/L and 250 +/- mu mol/L). When the patie nts with ARDS (both ARDS only and with sepsis) recovered, their urine H2O2 concentration did not differ from the control groups (healthy don ors and patients without ARDS). Conclusion: Lung injury scores did not differentiate patients with ARDS and sepsis from patients with ARDS o nly during the first 10 days in the ICU; however, urine H2O2 levels we re significantly greater in the patients with ARDS and sepsis. Moreove r despite no initial difference in lung injury, patients who did not s urvive ARDS and sepsis had consistently greater urine H2O2 concentrati on 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. Furthermor e, these studies demonstrate that urine H2O2 may be a useful analyte t o differentiate the severity of oxidant processes in patients with ARD S and sepsis albeit the prognosis appears to be survival or nonsurviva l.