The association of endothelial injury and systemic inflammation with perioperative myocardial infarction

Background Major surgery predisposes to endothelial glycocalyx injury. Endothelial glycocalyx injury associates with cardiac morbidity, including spontaneous myocardial infarction. However, the relation between endothelial glycocalyx injury and the development of perioperative myocardial infarction remains unknown. Methods Fifteen perioperative myocardial infarction patients and 60 propensity-matched controls were investigated in this prospective study. The diagnosis of perioperative myocardial infarction was based on repeated cardiac troponin T measurements, electrocardiographs and recordings of ischaemic signs and symptoms. We measured endothelial glycocalyx markers - soluble thrombomodulin, syndecan-1 and vascular adhesion protein 1 - and an inflammatory marker, namely interleukin-6, preoperatively and 6 h and 24 h postoperatively. We calculated the areas under the receiver operating characteristics curves (AUCs) to compare the performances of the different markers in predicting perioperative myocardial infarction. The highest value of each marker was used in the analysis. Results The interleukin-6 concentrations of perioperative myocardial infarction patients were significantly higher preoperatively and 6 and 24 h postoperatively (P = 0.002, P = 0.002 and P = 0.001, respectively). The AUCs (95% confidence intervals) for the detection of perioperative myocardial infarction were 0.51 (0.34-0.69) for soluble thrombomodulin, 0.63 (0.47-0.79) for syndecan-1, 0.54 (0.37-0.70) for vascular adhesion protein 1 and 0.69 (0.54-0.85) for interleukin-6. Conclusions Systemic inflammation, reflected by interleukin-6, associates with cardiac troponin T release and perioperative myocardial infarction. Circulating interleukin-6 demonstrated some potential to predict perioperative myocardial infarction, whereas endothelial glycocalyx markers did not.Peer reviewe

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk

Early prolonged neutrophil activation in critically ill patients with sepsis

We hypothesised that plasma concentrations of biomarkers of neutrophil activation and pro-inflammatory cytokines differ according to the phase of rapidly evolving sepsis. In an observational study, we measured heparin-binding protein (HBP), myeloperoxidase (MPO), IL-6 and IL-8 in 167 sepsis patients on intensive care unit admission. We prospectively used the emergence of the first sepsis-associated organ dysfunction (OD) as a surrogate for the sepsis phase. Fifty-five patients (of 167, 33%) developed the first OD > 1 h before, 74 (44%) within +/- 1 h, and 38 (23%) > 1 h after intensive care unit admission. HBP and MPO were elevated at a median of 12 h before the first OD, remained high up to 24 h, and were not associated with sepsis phase. IL-6 and IL-8 rose and declined rapidly close to OD emergence. Elevation of neutrophil activation markers HBP and MPO was an early event in the evolution of sepsis, lasting beyond the subsidence of the pro-inflammatory cytokine reaction. Thus, as sepsis biomarkers, HBP and MPO were not as prone as IL-6 and IL-8 to the effect of sample timing.Peer reviewe

Acute Kidney Injury After Cardiac Surgery by Complete KDIGO Criteria Predicts Increased Mortality

Objectives: Acute kidney injury (AKI) occurs frequently after cardiac surgery and is associated with increased mortality. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria for diagnosing AKI include creatinine and urine output values. However, the value of the latter is debated. The authors aimed to evaluate the incidence of AKI after cardiac surgery and the independent association of KDIGO criteria, especially the urine output criterion, and 2.5-year mortality. Design: Prospective, observational, cohort study. Setting: Single-center study in a university hospital. Participants: The study comprised 638 cardiac surgical patients from September 1, 2011, to June 20, 2012. Interventions: None. Measurements and Main Results: Hourly urine output, daily plasma creatinine, risk factors for AKI, and variables for EuroSCORE II were recorded. AKI occurred in 183 (28.7%) patients. Patients with AKI diagnosed using only urine output had higher 2.5-year mortality than did patients without AKI (9/53 [17.0%] v 23/455 [5.1%], p = 0.001). AKI was associated with mortality (hazard ratios [95% confidence intervals]: 3.3 [1.8-6.1] for KDIGO I; 5.8 [2.7-12.1] for KDIGO 2; and 7.9 [3.5-17.6]) for KDIGO 3. KDIGO stages and AKI diagnosed using urine output were associated with mortality even after adjusting for mortality risk assessed using EuroSCORE II and risk factors for AKI. Conclusions: AKI diagnosed using only the urine output criterion without fulfilling the creatinine criterion and all stages of AKI were associated with long-term mortality. Preoperatively assessed mortality risk using EuroSCORE II did not predict this AKI-associated mortality. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Association of oliguria with the development of acute kidney injury in the critically ill

Urine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria(<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy(RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%)developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6–12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h.Thus, our findings underlie the importance of hourly UO measurements