Matthias Klingele

Risk factors for nonocclusive mesenteric ischemia after elective cardiac surgery.

OBJECTIVEnNonocclusive mesenteric ischemia (NOMI) may occur after cardiopulmonary bypass. It is crucial to early identify patients who are at risk of developing this complication. The aim of this prospective study was to evaluate perioperative risk factors in a large cohort of patients undergoing elective cardiac surgery.nnnMETHODSnFrom January 1, 2010, to March 31, 2011, all patients scheduled for elective cardiac surgery were screened for participation in this trial. If NOMI was suspected, arterial angiography was performed. NOMI and non-NOMI patients were compared with respect to all variables assessed in this study. Additionally, odds ratios were calculated. Linear discriminant analyses as well as logistic regression analyses were performed to develop a model that identifies patients at risk for developing NOMI.nnnRESULTSnEight hundred sixty-five patients were included in the study, of whom 78 developed NOMI. Among preoperative parameters, renal insufficiency, diuretic therapy, and age >70 years showed the highest odds ratios for postoperative NOMI. The highest odds ratios for development of NOMI were observed with postoperative variables. In particular, the need for intra-aortic balloon pump support and serum lactate concentrations >5 mmol/L proved to be serious risk factors. Using a linear discriminant analysis with 7 variables, 92.3% of patients were correctly classified (sensitivity 76.9%, specificity 93.8%).nnnCONCLUSIONSnA high index of suspicion for NOMI in patients with the above-mentioned risk factors may decrease the diagnostic and therapeutic delay. To identify at-risk patients the developed risk equation is a useful tool with a high specificity.

Total-to-ionized calcium ratio predicts mortality in continuous renal replacement therapy with citrate anticoagulation in critically ill patients.

IntroductionRegional citrate anticoagulation is safe, feasible and increasingly used in critically ill patients on continuous renal replacement therapy (CRRT). However, in patients with hepatic or multi-organ dysfunction, citrate accumulation may lead to an imbalance of calcium homeostasis. The study aimed at evaluating the incidence and prognostic relevance of an increased total to ionized calcium ratio (T/I Ca2+ ratio) and its association to hepatic dysfunction.MethodsWe performed a prospective observational study on n = 208 critically ill patients with acute kidney injury (AKI) and necessity for CRRT with regional citrate anticoagulation (CRRT-citrate) between September 2009 and September 2011. Critical illness was estimated by Simplified Acute Physiology Score II; hepatic function was measured with indocyanine green plasma disappearance rate. After achieving a steady state of calcium homeostasis patients were classified into tertiles according to the T/I Ca2+ ratio (<2.0 versus 2.0 - 2.39 versus ≥2.4).ResultsThe T/I Ca2+ ratio was determined as an independent predictor for 28-day mortality in critically ill patients with AKI on CRRT-citrate confirmed by receiver operating characteristics and multivariate analysis (Area under the curve 0.94 ± 0.02; p<0.001). A T/I Ca2+ ratio ≥2.4 independently predicted a 33.5-fold (p<0.001) increase in 28-day mortality-rate. There was a significant correlation between the T/I Ca2+ ratio and the hepatic clearance (p<0.001) and the severity of critical illness (p<0.001). The efficacy and safety of citrate anticoagulation, determined by blood urea nitrogen, mean filter patency and bleeding episodes, were not significantly different between the tertiles.ConclusionsIn patients on CRRT-citrate T/I Ca2+ ratio is closely related to the clinical outcome and emerged as an independent predictor of 28-day mortality. Larger studies are required to define the cut-off and predictive value for the T/I Ca2+ ratio. This ratio is associated with hepatic and/or multi-organ dysfunction and therefore an important therapeutic target.

Single FGF-23 Measurement and Time-Averaged Plasma Phosphate Levels in Hemodialysis Patients

BACKGROUND AND OBJECTIVESnPlasma phosphate levels display considerable intraindividual variability. The phosphatonin fibroblast growth factor 23 is a central regulator of plasma phosphate levels, and it has been postulated to be a more stable marker than conventional CKD-mineral and bone disorder parameters. Thus, fibroblast growth factor 23 has been hypothesized to reflect time-averaged plasma phosphate levels in CKD patients.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnAmong 40 patients from the outpatient dialysis center, serial measurements of plasma calcium and phosphate (before every dialysis session) as well as C-terminal fibroblast growth factor 23, parathyroid hormone, and alkaline phosphatase (one time weekly) were performed over a study period of 4 weeks in November and December of 2011. Intraindividual variability of repeated plasma fibroblast growth factor 23 measurements compared with other CKD-mineral and bone disorder markers was tested, and the association of a single plasma fibroblast growth factor 23 measurement with time-averaged plasma phosphate levels was analyzed.nnnRESULTSnAgainst expectations, intraindividual variability of fibroblast growth factor 23 (median coefficient of variation=27%; interquartile range=20-35) was not lower than variability of plasma phosphate (median coefficient of variation=15%; interquartile range=10-20), parathyroid hormone (median coefficient of variation=24%; interquartile range=15-39), plasma calcium (median coefficient of variation=3%; interquartile range=2-4), or alkaline phosphatase (median coefficient of variation=5%; interquartile range=3-10). Moreover, the correlation between the last fibroblast growth factor 23 measurement after 4 weeks and time-averaged plasma phosphate did not surpass the correlation between the last fibroblast growth factor 23 measurement and a single plasma phosphate value (r=0.67, P<0.001; r=0.76, P<0.001, respectively).nnnCONCLUSIONSnSurprisingly, fibroblast growth factor 23 was not more closely associated to time-averaged plasma phosphate levels than a single plasma phosphate value, and it did not show a lower intraindividual variability than other tested markers of CKD-mineral and bone disorder. Thus, fibroblast growth factor 23 should not be used in clinical practice as a reflector of time-averaged plasma phosphate levels.

Elevated endothelin-1 level is a risk factor for nonocclusive mesenteric ischemia

OBJECTIVEnNonocclusive mesenteric ischemia may occur after cardiac surgery, commonly in conjunction with the use of cardiopulmonary bypass. Some evidence suggests that endothelin-1 serum levels are increased in patients with mesenteric ischemia, but the association of endothelin-1 and nonocclusive mesenteric ischemia has not been studied. The objective was to investigate whether elevated levels of endothelin-1 could be found in patients exhibiting nonocclusive mesenteric ischemia.nnnMETHODSnIn an observational cohort study, nonocclusive mesenteric ischemia developed in 78 of 865 patients undergoing elective cardiac surgery. Control patients were identified from the cohort through 1:1 propensity score matching. Preoperative and postoperative endothelin-1 serum levels were determined by means of enzyme-linked immunosorbent assay. Odds ratios (with 95% confidence interval) were calculated by logistic regression analyses to determine the risk of endothelin-1 for the development of nonocclusive mesenteric ischemia.nnnRESULTSnPatients with nonocclusive mesenteric ischemia had higher preoperative (11.3 vs 9.3 pg/mL; P = .001) and postoperative (15.7 vs 11.1 pg/mL, P < .001) levels of endothelin-1 than the controls. The probability of developing nonocclusive mesenteric ischemia increased with each picogram/milliliter endothelin-1 level preoperatively (odds ratio, 1.29; 95% confidence interval, 1.12-1.49) and each picogram/milliliter postoperatively (odds ratio, 2.04; 95% confidence interval, 1.54-2.72). Receiver operating characteristic analyses showed that elevated endothelin-1 serum levels had a high accuracy to predict nonocclusive mesenteric ischemia (optimal cutoff value of 14.5 pg/mL, area under the curve of 0.77, sensitivity 51%, and specificity 94%).nnnCONCLUSIONSnEndothelin-1 seems to predispose patients undergoing cardiac surgery to develop nonocclusive mesenteric ischemia. In addition, it may be a useful marker to identify patients at risk for nonocclusive mesenteric ischemia after cardiac surgery.

A single preoperative FGF23 measurement is a strong predictor of outcome in patients undergoing elective cardiac surgery: a prospective observational study.

IntroductionSeveral scoring systems have been developed to predict postoperative mortality and complications in patients undergoing cardiac surgery. However, these computer-based calculations are time- and cost-intensive. A simple but highly predictive test for postoperative risk would be of clinical benefit with respect to increasingly scarce hospital resources. We therefore assessed the predictive power of fibroblast growth factor 23 (FGF23) measurement compared with an established scoring system.MethodsWe conducted a prospective interdisciplinary observational study at the Saarland University Medical Centre that included 859 patients undergoing elective cardiac surgery between January 2010 and March 2011 with a median follow-up after discharge of 822xa0days. We compared a single preoperative measurement of FGF23 as a prognostic tool with the 18 parameters comprising EuroSCORE II with respect to postoperative mortality, acute kidney injury, non-occlusive mesenteric ischemia, clinical course and long-term outcome.ResultsPreoperative FGF23 levels were highly predictive of postoperative outcome and complications. The predictive value of FGF23 for mortality in the receiver operating characteristic curve was greater than the EuroSCORE II (area under the curve: 0.800 versus 0.725). Moreover, preoperative FGF23 independently predicted postoperative acute kidney injury and non-occlusive mesenteric ischemia comparably to the EuroSCORE II. Finally, FGF23 was found to be an independent predictor of clinical course parameters, including duration of surgery, ventilation time and length of stay.ConclusionsIn patients undergoing elective cardiac surgery, a simple preoperative FGF23 measurement is a powerful indicator of surgical mortality, postoperative complications and long-term outcome. Its utility compares to the widely used EuroSCORE II.

Acute kidney injury prediction in cardiac surgery patients by a urinary peptide pattern: a case-control validation study

BackgroundAcute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease.In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis.MethodsUrine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls.ResultsFrom the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95xa0% confidence interval: 0.72–0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1).ConclusionsThis study gives further proof for the general applicability of our proteomic multimarker model for early and accurate prediction of AKI irrespective of its underlying disease cause.

Elevated procalcitonin in patients after cardiac surgery: a hint to nonocclusive mesenteric ischemia.

BACKGROUNDnNonocclusive mesenteric ischemia (NOMI) can occur after cardiac surgery, commonly in conjunction with use of cardiopulmonary bypass. Some evidence suggests that serum procalcitonin (PCT) levels are increased in patients with mesenteric ischemia; however, an association between PCT and NOMI has not yet been studied. The current study investigates whether elevated serum PCT levels are found in patients exhibiting NOMI.nnnMETHODSnIn an observational cohort study of 865 patients undergoing elective cardiac surgery, 78 experienced NOMI. Preoperative and postoperative PCT levels were determined by means of enzyme-linked immunosorbent assay. Odds ratios and 95% confidence intervals were calculated by logistic regression analyses to predict accuracy of PCT in identifying patients with NOMI. Additional models were calculated, adjusting for potential confounders.nnnRESULTSnPatients with NOMI had higher postoperative PCT levels than control patients (20.8 ± 3.2 ng/mL versus 2.3 ± 1.1 ng/mL; p < 0.001). Likelihood of experiencing NOMI increased with each nanogram per milliliter rise in postoperative PCT level (odds ratio, 2.61; 95% confidence interval, 2.05 to 3.32). Receiver operating characteristic analyses showed elevated serum PCT levels to accurately predict occurrence of NOMI (optimal cutoff value, 6.6 ng/mL; area under the curve, 0.94; sensitivity, 71%; specificity, 94%).nnnCONCLUSIONSnPostoperative measurement of PCT seems useful to improve the clinical and noninvasive identification of patients with NOMI after cardiac surgery.

A Scoring-System for Angiographic Findings in Nonocclusive Mesenteric Ischemia (NOMI): Correlation with Clinical Risk Factors and its Predictive Value

AbstractPurposeThis study was designed to evaluate the clinical value of a standardized angiographic scoring system in patients with nonocclusive mesenteric ischemia (NOMI).nMethodsSixty-three consecutive patients (mean age: 73xa0±xa08xa0years) with suspect of NOMI after cardiac or major thoracic vessel surgery underwent catheter angiography of the superior mesenteric artery. Images were assessed by two experienced radiologists on consensus basis using a scoring system consisting of five categories, namely vessel morphology, reflux of contrast medium into the aorta, contrasting and distension of the intestine, as well as the time to portal vein filling. These were correlated to previously published risk factors of NOMI and outcome data.ResultsThe most significant correlation was found between the vessel morphology and death (pxa0<xa00.001) as well as reflux of contrast medium into the aorta and death (pxa0=xa00.005). Significant correlation was found between delayed portal vein filling and preoperative statin administration (pxa0=xa00.011), previous stroke (pxa0=xa00.033), and renal insufficiency (pxa0=xa00.043). Reflux of contrast medium correlated significantly with serum lactate >10xa0mmol/L (pxa0=xa00.046). The overall angiographic score correlated with death (pxa0=xa00.017) and renal insufficiency (pxa0=xa00.02). The ROC-analysis revealed that a score of ≥3.5 allows for identifying patients with increased perioperative mortality with a sensitivity of 85.7xa0% and a specificity of 49xa0%. With the use of a simplified score (vessel morphology, reflux of contrast medium into the aorta, and time to portal vein filling), specificity was increased to 71.4xa0%.ConclusionsThe applied scoring system allows standardized interpretation of angiographic findings in NOMI patients. Beyond that the score seems to correlate well with risk factors of NOMI and outcome.

Presepsin (sCD14-ST) Is a Novel Marker for Risk Stratification in Cardiac Surgery Patients

Background: Presepsin (soluble cluster-of-differentiation 14 subtype [sCD14-ST]) is a humoral risk stratification marker for systemic inflammatory response syndrome and sepsis. It remains unknown whether presepsin can be used to stratify risk in elective cardiac surgery. The authors therefore determined the usefulness of presepsin for risk stratification in patients having elective cardiac surgery. Methods: Eight hundred fifty-six cardiac surgical patients were prospectively studied. Preoperative plasma concentrations of presepsin, procalcitonin, N-terminal pro–hormone natriuretic peptide, cystatin C, and the additive European System of Cardiac Operative Risk Evaluation 2 were compared to mortality at 30 days (primary outcome), 6 months, and 2 yr. Discrimination was assessed with C statistic. Logistic regression analysis was used to calculate univariable and multivariable odds ratios. Results: Thirty-day mortality was 3.2%, 6-month mortality was 6.1%, and 2-yr mortality was 10.4% across the population. Median preoperative presepsin concentrations were significantly greater in 30-day nonsurvivors than in survivors: 842 pg/ml (interquartile range, 306 to 1,246) versus 160 pg/ml (interquartile range, 122 to 234); difference, 167 pg/ml (interquartile range, 92 to 301; P < 0.001). The results were similar for 6-month and 2-yr mortality. Compared to the European System of Cardiac Operative Risk Evaluation 2, presepsin concentration provided better discrimination for postoperative mortality at all follow-up periods, including 30 days (C statistic 0.88 vs. 0.74), 6 months (0.87 vs. 0.76), and 2 yr (0.81 vs. 0.74). Presepsin also provided better discrimination than cystatin C, N-terminal pro–hormone natriuretic peptide, or procalcitonin. Elevated presepsin remained an independent risk predictor after adjustment for potential confounding factors. Conclusions: Elevated preoperative plasma presepsin concentration is an independent predictor of postoperative mortality in elective cardiac surgery patients and is a stronger predictor than several other commonly used assessments.

Vasopressin as Therapy During Nonocclusive Mesenteric Ischemia

BACKGROUNDnVasopressin is used as an adjunct to norepinephrine to support blood pressure in vasodilatory shock after cardiopulmonary bypass (CPB). In this study, we report our observation of vasopressin treatment in 11 patients with nonocclusive mesenteric ischemia (NOMI).nnnMETHODSnIn an observational cohort study, 78 patients were studied after having been treated for NOMI with intraarterial iloprost infusion after elective cardiac operation. All patients received norepinephrine as vasopressor for marked vasodilation. In 11 patients mean arterial pressure could not be maintained with norepinephrine alone (≤0.4 μg · kg(-1) · min(-1)), and vasopressin was given in addition to norepinephrine as a rescue therapy. The 11 patients (Vaso) and the remaining 67 patients (Nor) were analyzed for clinical improvement after initiation of NOMI treatment, on the following days 1 and 2, and for hospital survival. Intestinal perfusion was controlled by mesenteric angiography.nnnRESULTSnBefore initiation of NOMI treatment Vaso patients had significantly higher doses of norepinephrine than the Nor patients (Vaso, 0.65 ± 0.20 μg · kg(-1) · min(-1); Nor, 0.20 ± 0.13 μg · kg(-1) · min(-1); p < 0.001), and their diagnostic score of the angiography was higher (Vaso, 5.4 ± 1.1 points; Nor, 3.5 ± 2.1 points; pxa0= 0.004). After 2 days of NOMI treatment, Vaso patients had improved intestinal perfusion in the control angiography (Vaso, 3.8 ± 1.5 points) and significantly lower doses of norepinephrine than the Nor patients (Vaso, 0.28 ± 0.12 μg · kg(-1) · min(-1); Nor, 0.53 ± 0.34 μg · kg(-1) · min(-1); pxa0= 0.002). All patients survived in the Vaso group; in the Nor group, 17 of 67 patients died in the hospital.nnnCONCLUSIONSnVasopressin administration during NOMI treatment after CPB seems to improve small intestine perfusion and appears be to associated with improved hospital survival.