Remote ischemic preconditioning (RIPC) and postconditioning (RpostC) have protective effects on ischemia and reperfusion injury. The effects have been reported to activate heme oxygenase-1 (HO-1) and attenuate nuclear factor kappa B (NF-κB) and subsequently reduce systemic inflammation. Ischemic preconditioning prevented inflammatory responses by modulating HO-1 expression in endotoxic shock model. Therefore, we investigated whether RpostC could have protective effects on lipopolysaccharide (LPS)-induced systemic inflammation.

Background: The renoprotective effects of erythropoietin (EPO) are well-known; however, the optimal timing of EPO administration remains controversial. Red blood cell (RBC) transfusion is an independent risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). We aimed to evaluate the efficacy of EPO on CSA-AKI and RBC transfusion according to the timing of administration. Methods: We searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials. The primary outcome was the incidence of CSA-AKI following perioperative EPO administration, and the secondary outcomes were changes in serum creatinine, S-cystatin C, S-neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, length of hospital and intensive care unit (ICU) stay, volume of RBC transfusion, and mortality. The subgroup analysis was stratified according to the timing of EPO administration in relation to surgery. Results: Eight randomized controlled trials with 610 patients were included in the study. EPO administration significantly decreased the incidence of CSA-AKI (odds ratio: 0.60, 95% confidence interval [CI]: 0.43–0.85, P = .004; I ² = 52%; P for heterogeneity = .04), intra-operative RBC transfusion (standardized mean difference: −0.30, 95% CI: −0.55 to −0.05, P = .02; I ² = 15%, P for heterogeneity = .31), and hospital length of stay (mean difference: −1.54 days, 95% CI: −2.70 to −0.39, P = .009; I ² = 75%, P for heterogeneity = .001) compared with control groups. Subgroup analyses revealed that pre-operative EPO treatment significantly reduced the incidence of CSA-AKI, intra-operative RBC transfusion, serum creatinine, and length of hospital and ICU stay. Conclusion: Pre-operative administration of EPO may reduce the incidence of CSA-AKI and RBC transfusion, but not in patients administered EPO during the intra-operative or postoperative period. Therefore, pre-operative EPO treatment can be considered to improve postoperative outcomes by decreasing the length of hospital and ICU stay in patients undergoing cardiac surgery.

Ko E, et al. J Korean Med Sci. 2022 Feb;37(9):e71. https://doi.org/10.3346/jkms.2022.37.e71

BACKGROUND: Sepsis is a medical emergency during which early detection is closely associated with mortality. In sepsis, red blood cell (RBC) abnormalities have been reported. However, it is not known how early RBC abnormalities are expressed compared with various clinical manifestations used in sepsis-related organ failure assessment (SOFA). OBJECTIVE: Therefore, using a lipopolysaccharide (LPS)-induced sepsis model we investigated the clinical significance of RBC abnormalities as an early indicator in the detection of septic injury compared with clinical variables. METHODS: Sprague-Dawley rats received LPS (20 mg/kg) intraperitoneally. Aggregation indices (AIs) and aggregation half-time (T1/2), and elongation indices (EI _max) were measured. Clinical data-related SOFA and lactate were measured at 2 h, 4 h, 8 h and 12 h after LPS injection. RESULTS: AIs increased at 4 h, and T1/2 decreased at 2 h after LPS injection. Platelet counts decreased at 4 h, and lactate increased at 2 h after LPS injection. AIs showed strong correlations with T1/2 and platelets, EI _max increased at 2 h after LPS injection, while EI _max had a positive correlation with lactate. CONCLUSIONS: RBC aggregation appears to be an early indicator of clinical deterioration in sepsis and may represent a diagnostic indicator in sepsis.

Pneumoperitoneum with an intra-abdominal pressure (IAP) of 14 mmHg is known to decrease renal function. Robotic-assisted radical prostatectomy (RARP) requires an IAP of more than 15 mmHg for operation. Therefore, we retrospectively investigated whether patients who underwent RARP experienced renal insufficiency during the postoperative period (at postoperative days 7 and 30). One hundred patients who underwent RARP were enrolled in this study. Preoperative serum blood urea nitrogen (BUN) and serum creatinine (Cr) levels were measured. Creatinine clearance (CrCl) was calculated using the Cockcroft and Gault formula. CrCl was calculated at 1 day before surgery (baseline), 2 hr postoperatively, and at 1, 3, 7, and 30 days postoperatively (POD 1, POD 3, POP 7, and POD 30). Patients were assigned to abnormal CrCl (n = 52) or normal CrCl groups (n = 48) on the basis of these measurements. Significant inter-group differences in BUN, Cr, and CrCl were observed at all postoperative time points. BUN and Cr decreased significantly at postoperative 2 hr and POD 1, 3, and 7 versus baseline in both groups, whereas CrCl increased significantly at postoperative 2 hr and POD 1, 3, and 7 versus baseline in both groups. However, BUN, Cr, and CrCl were similar at POD 30 and preoperatively in the two groups. RAPR, which requires an IAP of 15-20 mmHg for more than 4 hr, does not induce renal dysfunction during the postoperative period, and even in those patients with an abnormal CrCl.

Objective: Acute lung injury is responsible for mortality in seriously ill patients. Previous studies have shown that systemic inflammation is attenuated by remote ischemic preconditioning (RIPC) via reducing nuclear factor-kappa B (NF-κB). Therefore, we investigated whether lipopolysaccharide (LPS)-induced indirect acute lung injury (ALI) can be protected by RIPC. Methods: RIPC was accomplished by 10 minutes of occlusion using a tourniquet on the right hind limb of mice, followed by 10 minutes of reperfusion. This process was repeated three times. Intraperitoneal LPS (20 mg/kg) was administered to induce indirect ALI. Inflammatory cytokines in bronchoalveolar lavage fluid were analyzed using an enzyme-linked immunosorbent assay. Pulmonary tissue was excised for histological examination, and for examining NF-κB activity and phosphorylation of inhibitor of κBα (IκBα). Results: NF-κB activation and LPS-induced histopathological changes in the lungs were significantly alleviated in the RIPC group. RIPC reduced phosphorylation of IκBα in lung tissue of ALI mice. Conclusions: RIPC attenuates endotoxin-induced indirect ALI. This attenuation might occur through modification of NF-κB mediation of cytokines by modulating phosphorylation of IκBα.