Use of argatroban: experiences in continuous renal replacement therapy in critically ill patients after cardiac surgery.

OBJECTIVES: Acute kidney injury requiring renal replacement therapy (RRT) is a common complication after cardiac surgery, complicated by suspected or proven heparin-induced thrombocytopenia (type II). The present study evaluated the use of argatroban as an anticoagulant during continuous RRT in the early period after cardiac surgery. Argatroban was compared with unfractionated heparin (UH) with respect to bleeding complications and the effectiveness of anticoagulation. METHODS: Patients requiring RRT after cardiac surgery from March 2007 to June 2009 were identified. The effectiveness of anticoagulation was measured indirectly by the duration of dialysis filter use. Bleeding was defined as clinical signs of blood loss or the need for transfusion. RESULTS: Of 94 patients, 41 received argatroban, 27 UH, and 26 required conversion from UH to argatroban. In all 3 subgroups, RRT was begun within a median postoperative period of 2.0 days. Similar levels of anticoagulation were achieved with the duration of the circuit and filter changed an average of 1.1 times daily during RRT. Liver function was comparable in all patients. Neither clinically relevant signs of bleeding nor significant differences in the hemoglobin levels or a requirement for transfusion were noted. However, the Simplified Acute Physiology Score II values during dialysis and mortality were significantly greater in the patients initially receiving argatroban compared with those who received UH alone (54 ± 2 vs 43 ± 3, P < .001; 71% vs 44%, P = .04). CONCLUSIONS: Argatroban can provide effective anticoagulation in postoperative cardiac patients receiving continuous RRT. Close monitoring and dose titration resulted in a comparable risk of bleeding for anticoagulation with both argatroban and heparin, regardless of the disease severity or impaired hepatic function.

Single FGF-23 measurement and time-averaged plasma phosphate levels in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Plasma 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 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. RESULTS: Against 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). CONCLUSIONS: Surprisingly, 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.

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

INTRODUCTION: Regional 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 Ca(2+) ratio) and its association to hepatic dysfunction. METHODS: We 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 Ca(2+) ratio (<2.0 versus 2.0 - 2.39 versus ≥ 2.4). RESULTS: The T/I Ca(2+) 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 Ca(2+) 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 Ca(2+) 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. CONCLUSIONS: In patients on CRRT-citrate T/I Ca(2+) 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 Ca(2+) ratio. This ratio is associated with hepatic and/or multi-organ dysfunction and therefore an important therapeutic target.