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To determine the effect on strong ion difference of citrate as an anticoagulant during continuous veno-venous hemofiltration (CVVH).ICU patients with renal failure and CVVH were included. Patients were treated with either nadroparin (N) or sodium citrate (C) as an anticoagulant. Strong ion difference (SID) apparent (SIDa) and SID effective (SIDe) and strong ion gap (SIG) were calculated at t = 0 and t = 24 h. Citrate concentration was measured in the citrate treated patients.Ten patients with N and nine with C were included. In both groups the SIDa did not change significantly. SIG decreased significantly with N (11.4 ± 4.2 to 4.0 ± 3.1 meq/l; p = 0.005) but not with C (9.3 ± 1.9 to 8.1 ± 2.4 meq/l; p = 0.097). The decrease was significantly greater for N compared to C; p = 0.014. This is reflected by the SIDe which increased significantly (p = 0.022) more from 24.7 ± 4.5 to 32.9 ± 3.9 (p = 0.005) for N and from 26.3 ± 5.8 to 29.6 ± 1.6 for C (p = 0.058).Citrate anticoagulation results in a persistently high SIG during CVVH compared to nadroparin. This is associated with the presence of unmeasured anions such as citrate in the systemic circulation.In patients with citrate and nadroparin CVVH the SIDa did not change.In patients with citrate CVVH SIDe increased compared to nadroparin.In patients with nadroparin CVVH SIG decreased more than in citrate CVVH.Citrate CVVH leads to a greater SIG than nadroparin CVVH.