Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial.

IMPORTANCE: No effective pharmaceutical agents have yet been identified to treat acute kidney injury after cardiac surgery. OBJECTIVE: To determine whether fenoldopam reduces the need for renal replacement therapy in critically ill cardiac surgery patients with acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study from March 2008 to April 2013 in 19 cardiovascular intensive care units in Italy. We randomly assigned 667 patients admitted to intensive care units after cardiac surgery with early acute kidney injury (≥50% increase of serum creatinine level from baseline or oliguria for ≥6 hours) to receive fenoldopam (338 patients) or placebo (329 patients). We used a computer-generated permuted block randomization sequence for treatment allocation. All patients completed their follow-up 30 days after surgery, and data were analyzed according to the intention-to-treat principle. INTERVENTIONS: Continuous infusion of fenoldopam or placebo for up to 4 days with a starting dose of 0.1 µg/kg/min (range, 0.025-0.3 µg/kg/min). MAIN OUTCOMES AND MEASURES: The primary end point was the rate of renal replacement therapy. Secondary end points included mortality (intensive care unit and 30-day mortality) and the rate of hypotension during study drug infusion. RESULTS: The study was stopped for futility as recommended by the safety committee after a planned interim analysis. Sixty-nine of 338 patients (20%) allocated to the fenoldopam group and 60 of 329 patients (18%) allocated to the placebo group received renal replacement therapy (P = .47). Mortality at 30 days was 78 of 338 (23%) in the fenoldopam group and 74 of 329 (22%) in the placebo group (P = .86). Hypotension occurred in 85 (26%) patients in the fenoldopam group and in 49 (15%) patients in the placebo group (P = .001). CONCLUSIONS AND RELEVANCE: Among patients with acute kidney injury after cardiac surgery, fenoldopam infusion, compared with placebo, did not reduce the need for renal replacement therapy or risk of 30-day mortality but was associated with an increased rate of hypotension. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00621790.

Effects of dermatan sulfate for anticoagulation in continuous renal replacement therapy.

BACKGROUND: Dermatan sulfate (DS) is a natural glycosaminoglycan with a unique mechanism of action on the coagulation system. Unlike unfractionated heparin (UFH), DS selectively inhibits thrombin, does not inhibit factor Xa, is effective on both free and fibrin-bound thrombin and does not interfere with platelets. This study represents the first experience using DS as anticoagulant in patients on continuous renal replacement therapy (CRRT). METHODS: A total of 147 patients in our intensive care unit who developed acute renal failure after cardiovascular surgery were on CRRT according to the same protocol: machine, Gambro Prisma; filter, AN69, 0.9 m2; QB, 150 ml/min; QD, 2,000 ml/hour; and Q(Infusate), 500 ml/hour. In a retrospective cohort of 100 patients, anticoagulation was performed with UFH (UFH-CRRT): initial bolus of 530 +/- 363 IU, then i.v. infusion of 598 +/- 261 IU/hour. A prospective cohort of 47 patients received DS (DS-CRRT) as a 150-mg bolus followed by a 13.5 +/- 3 mg/hour infusion. Hematology tests were performed at baseline and during CRRT; filter lifetime was measured from the start to filter clotting. RESULTS: Median filter lifetime was 58 hours in DS-CRRT vs. 47 hours in UFH-CRRT (p<0.001). No differences emerged in basal hematology and hemostasis tests between groups. During CRRT, DS produced a smaller activated partial thromboplastin time increase than UFH (p<0.01). Platelet count exhibited a comparable small decline in both DS-CRRT and UFH-CRRT (p<0.01). No significant bleeding episodes occurred during DS-CRRT. In-hospital mortality was similar in the 2 cohorts. CONCLUSIONS: DS can be suggested as an anticoagulant for CRRT in patients who develop acute renal failure following major cardiovascular surgery.

Fenoldopam reduces the incidence of renal replacement therapy after cardiac surgery.

OBJECTIVE: To investigate whether a continuous 48-hour infusion of fenoldopam, 0.1 mug/kg/min, reduced the need for renal replacement therapy in patients with acute renal injury after cardiac surgery. DESIGN: Case-matched study. SETTING: Teaching hospital. PARTICIPANTS: Ninety-two patients. INTERVENTIONS: Patients who developed acute renal injury (defined as serum creatinine doubling or oliguria) after cardiac surgery received a continuous infusion of fenoldopam, 0.1 mug/kg/min, (46 patients) for 48 hours. They were case matched with 46 patients who developed acute renal injury, had similar baseline characteristics, and received standard treatment (hemodynamic support to obtain a mean arterial pressure >60 mmHg, fluid administration to increase central venous pressure >10 mmHg, and loop diuretics to maintain a urine output >0.5 mL/kg/h). Renal replacement therapy was started when acute renal injury became oligoanuric, when serum creatinine increased >4 mg/dL or 3 times basal value, or in the presence of severe hyperkalemia (K >6.5 mmol/L) or severe acidemia (pH < 7). MEASUREMENTS AND MAIN RESULTS: Patients in the fenoldopam group had a reduced need for renal replacement therapy (8 patients, 17%) with respect to case-matched controls (18 patients, 39%; p = 0.037). The length of intensive care unit stay (median [interquartile range]) was similar in the 2 groups: fenoldopam group, 5 days (3-9 days), and control group, 10 days (3-16 days, p = 0.15). CONCLUSIONS: Given the limitations of case-matched studies, fenoldopam may be useful in avoiding renal replacement therapy in patients who develop acute renal injury after cardiac surgery.

[Hospital mortality at a cardiosurgical unit in Torino: international comparisons and time trend]. / Mortalità ospedaliera in una unità di cardiochirurgia di Torino: confronti internazionali e andamento temporale.

OBJECTIVE: To compare hospital mortality in a cardiac surgery unit with external data and to assess changes in time (patients undergoing surgery in two different periods). MATERIALS AND METHODS: Data on risk factors for hospital mortality were collected from clinical records (retrospectively for the first period and prospectively for the second) for all patients undergoing open heart surgery at the Heart Surgery Unit of the University of Turin (Italy) during 1991 and 1995 (n = 1794) and 1999 (n = 892). Comparisons of in-hospital mortality, expressed as Standardized Mortality Ratios (SMR), were adjusted for risk factors defined according to EuroSCORE (European System for Cardiac Operative Risk Evaluation). RESULTS: In the first and second period, complete information on all the 17 EuroSCORE items was available for 58.3% and 89.6% patients respectively. After exclusion of patients with one or more missing data, observed and expected numbers of death were found to be very similar, with SMRs ranging between 0.82 (isolated bypass in the second period) and 1.06 ("other" surgery in the first period). Mortality was higher among patients with missing data, but at least in 1999 the latter had a limited impact on the overall estimates. Compared to the first period, mortality was reduced during 1999 (from 5.9% to 5.4%), in particular for isolated bypass (from 4.4% to 3.4%). CONCLUSIONS: In the unit under investigation, hospital mortality following heart surgery was similar to that predicted from EuroSCORE and seemed to be lower in 1999 than in 1991-95, particularly for isolated bypass. Incompleteness of data on individual risk factors may have been a source of bias, especially when data were collected retrospectively.

[The effects of continuous renal replacement therapy (CRRT) and intermittent haemodialysis (IHD) in the treatment of dabigatran overdose. Case report]. / CRRT e HD standard nel sovradosaggio di Dabigatran.

A 85-year-old man, with CKD (e-GFR 35 mL/min), had been given Dabigatran (a direct thrombin inhibitor) at 110 mg daily dose because of atrial fibrillation. Due to intercurrent diarrhea and dehydration, renal function worsened (e-GFR 11 mL/min) and Dabigatran excretion decreased, thereby inducing drug overload. In this case, Dabigatran must be removed by dialysis, but the most appropriate schedule is still undefined. The effects of both continuous haemodiafiltration (CVVHDF) and intermittent haemodialysis (IHD) on plasma Dabigatran (Echarin Chromogenic Assay) were reported. Dialysis clearance of Dabigatran was reported as ratio to urea clearance (Dab/Urea(Cl)). Coagulation was assessed by both DOA-aPTTratio and Thrombin Time-ratio (TTratio). Dabigatran was elevated at 597 ng/mL predialysis (bleeding threshold being 30 ng/mL), and decreased to 96 ng/mL (-84%) after 20 hours of CVVHDF (Urea(Cl) = 67 mL/min). Dab/Urea(Cl) was 0.49. Three hours after dialysis, Dabigatran rebounded to 208 ng/mL. On IHD (Urea(Cl)=238 mL/min), predialysis Dabigatran was 52 ng/mL and decreased to 8 ng/mL (-85%) after 3.5 hours of treatment. Dab/Urea(Cl) was 0.47. Fourteen hours later, Dabigatran rebounded at 19 ng/mL. There was a positive correlation between Dabigatran and TTratio (r = 0.92; p<0.0001), whereas DOA-aPTT did not increase above 2.5 times the reference values, even in face of the highest values of Dabigatran. Therefore, TTratio is more reliable than DOA-aPTT in detecting Dabigatran overdose. Post-dialysis rebound of Dabigatran occurred also with CVVHDF, thereby suggesting that accurate monitoring of both Dabigatran levels and bleeding risk are mandatory, also after long-lasting dialysis sessions.

Safe management of cesarean section in a patient of Eisenmenger syndrome.

We report our experience of a 29-year-old female with a complete atrio-ventricular septal defect leading to a single ventricle physiology and Eisenmenger syndrome. The patient successfully underwent spinal anesthesia for cesarean section in the 31 st week of pregnancy. A multidisciplinary approach involving cardiologist, cardiac surgeon, obstetrician, and anesthesiologist was utilized to achieve a safe pregnancy and cesarean for the delivery of the baby. A close clinical assessment is required, especially during the third trimester when the risk of acute right ventricular dysfunction increases. The use of extracorporeal membrane oxygenation (ECMO) (as a bridge to recovery or bridge to salvage) was planned to support oxygenation and circulation in case of acute biventricular dysfunction. The delivery/cesarean section was performed in a cardiac surgery operating room, and to reduce the time-frame for ECMO institution the femoral vessels were exposed surgically before the cesarean section.