Citrate Versus Heparin in Continuous Renal Replacement Therapy :

Citrate Versus Heparin in Continuous Renal Replacement Therapy : Effect on Cardiovascular System and Clot Circuit in Critically Ill Patients

King Chulalongkorn Memorial Hospital, Chiang Mai University, Department of Medicine, Somdech Phra Pinklao Hospital, Bangkok, Thailand.

This study is a prospective, multicenter, open-label randomized trial comparing regional citrate anticoagulation (RCA) with heparin-free protocol. The function mode was continuous venovenous hemodiafiltration (CVVHDF) in post-dilution mode. The investigators measured hemodynamic changes at certain time points after starting CRRT (0, 6, 12, 24, 48, 72 hr).Levels of inflammatory cytokine (IL-1β, IL-6, IL-8, IL-10 and TNF-ɑ) were measured at day 1 and day 3

Twenty patients were randomized into heparin group and 11 patients were in citrate group. The cardiac performance were not significantly different between 2 groups at every time point. The inflammatory cytokines declined similarly in both treatment arms. The maximum filter survivial time was longer in a RCA group but not reach statistically significant (44.64±26.56 hr vs p=0.693 in citrate and heparin free group respectively).There was no serious side effects dung both treatment arm even in the group of liver dysfunction patients.

systemic random sampling (block of four). Group A was the citrate group while group B was heparin- free method.

The RCA group CRRT were performed with Prisma flex or (Baxter Healthcare/Gambro Spain) or Informed machine with citrate pump. The function mode was continuous venovenous hemodiafiltration (CVVHDF) in postdilution mode with ST 150 filter sets. The substitution fluid was Accusol or Prismocal B22 .The dose of dialysis was 20-25 ml/kg/hr with blood flow 150-200 ml/min. Trisodium citrate solution (4%,136mmol/L) was infused into the arterial line prior to the blood pump at a dose of 4 mmol/L of plasma flow. Calcium chloride (5% 340 mmol/L elemental calcium) was infused into the venous return to maintain systemic ionized calcium in the normal range (0.99-1.30 mmol/L) and the targets values for ionized calcium (iCa2+) after the dialysis membrane were 0.25-0.35 mmol/L. The rale of calcium infusion was adjusted in a timely manner based on repeated measurements of calcium concentration

The heparin- free group The circuit was periodically flushed with 50 ml saline via access limb every 30 minutes .When pre-filter pressure started to rise, additional saline flushes would be given.

The investigators collected patient's plasma at study start (day 0) and at day 3, 5, 7, 14, 28) .Samples were used to measure inflammatory markers (Il 6, IL 8, IL 10 and TNFα) . . Markers of dialysis efficiency (BUN, creatinine) and other parameters related to AKI (acid base status, calcium, phosphorus, hemoglobin). The recorded variables also included adverse events, dialysis clotting, hemodynamic status, duration of mechanical ventilation, inotropic support. The hemodynamic parameters were monitored by EV 1000 clinical platform .The investigators measured cardiac performance data, which includes cardiac output (CO), cardiac index (CI), stroke volume (SV), and stroke volume indexes (SVI). Moreover, it also provides information about systemic vascular resistance (SVR). Thus, patient hemodynamic parameters as mentioned above were measured at the following 6 time-point: after the initiation of CRRT (T1), every 6 hours later for 24 hours (T2, T3, T4, T5), and at hour-72 (T6).

Inclusion Criteria: need for CRRT, no contraindication to CRRT Exclusion Criteria: patients with previous history of chronic kidney disease (CKD) (baseline serum creatinine > 2 mg/dL (male) or > 1.5 mg/dL (female) history of renal transplantation known pregnancy previous dialysis within 30 days severe liver disease end stage heart disease or untreatable malignancy moribund patients with expected survival less than 30 days previous use of heparin or other anticoagulant, antiplatelet within 7 day except use for deep vein thrombosis active bleeding at the time of enrollment and/or severe coagulopathy receiving blood or blood components prior to enrollment hemoglobin less than 7.5 g/dL and/or platelet count less than 100,000/mm3 previous underlying clotting disorders such as hypercoagulable state severe malnutrition (Body mass index (BMI ) less than 18) underwent CRRT for other reasons besides acute kidney injury (AKI)

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