Oxidative stress, caloric intake and outcomes of critically ill patients

BACKGROUND: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. METHODS: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. RESULTS: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). CONCLUSIONS: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.