8-hydroxy-2--deoxyguanosine and Critical-Illness

The aim of this study was to investigate the patterns of oxidative stress in critically ill patients and the association with caloric intake and outcomes.. In this pre-planned sub-study of the PermiT (Permissive Underfeeding versus Target Enteral Feeding in Adult Critically Ill Patients Trial- ISRCTN68144998), we included patients expected to stay in the ICU for ≥14 days. Serum samples were collected on days 1, 3, 5, 7 and 14 of enrollment. We measured total anti-oxidant capacity (TAC), protein carbonyl concentration (a measure of protein oxidation) and 8-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-OHdG) (a measure of DNA oxidation). We used principal component analysis (PCA) and hierarchical cluster analysis (HCA) to group patients according to oxidative stress.. Principal component analysis identified 2 components that were responsible for 79% of the total variance, and cluster analysis grouped patients in three statistically distinct clusters. Majority of patients 78.6% (44/55) were included in cluster 1 with lowest TAC, protein carbonyl and 8-OHdG levels and cluster 2 which accounted for 16.1% (9/55) of patients had the highest levels of TAC and intermediate levels of protein carbonyl levels. Cluster 3 patients 5.4% (3/56) had the highest protein carbonyl levels. Incident renal replacement therapy was highest in cluster 2 (4/8, 50.0%), compared to cluster 1 (4/42, 9.5%) and cluster 3 (1/3, 33.3%, p 0.01). When adjusted to oxidative stress cluster membership, permissive underfeeding was not associated with 90-day mortality (adjusted odds ratio, aOR 1.37, 95% CI 0.36, 5.25, p 0.64) but was associated significantly with lower incident renal replacement therapy (aOR 0.02, 95% CI < 0.001, 0.57, p 0.02).. There are different distinct patterns of oxidative stress in critically ill patients. Incident renal replacement therapy was different among the three clusters. Our data suggest a protective effect of permissive underfeeding on incident renal replacement therapy that may differ by clusters of oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Antioxidants; APACHE; Blood Proteins; Critical Illness; Energy Intake; Enteral Nutrition; Female; Humans; Intensive Care Units; Male; Middle Aged; Odds Ratio; Oxidative Stress; Proteins

To determine whether urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients.. Clinical outcome study in an adult medical intensive care unit (ICU).. 85 consecutive septic patients (59 men, 26 women).. Patient characteristics and the clinical course were examined. Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality was 25.9% (22/85) and hospital mortality 38.8% (33/85). Survivors' APACHEII scores on days 1 and 3 and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0+/-7.1 vs. 25.9+/-8.0; day 3, 15.0+/-5.8 vs. 23.2+/-8.3; difference, 6.0+/-5.5 vs. 1.7+/-6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8+/-2.4 vs. 3.0+/-2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results.. This is a preliminary study. Excretion of urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, and the APACHE II score were correlated with the outcome of critically septic patients in medical ICU.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; APACHE; Biomarkers; Chromatography, Liquid; Critical Illness; Deoxyguanosine; Female; Humans; Male; Oxidative Stress; Radioisotope Dilution Technique; Sepsis; Tandem Mass Spectrometry