CLINICAL NEPHROLOGY TEACHING CASE Unexpected Severe Hypocalcemia During Continuous Venovenous Hemodialysis With Regional Citrate Anticoagulation Herwig-Ulf Meier-Kriesche, MD, Kevin W. Finkel, MD, Jeremy J. Gitomer, and Thomas D. DuBose, Jr, MD ● Citrate is known to induce acute hypocalcemia in patients undergoing liver transplantation during the anhepatic phase. We describe the case of a 71-year-old woman with fulminant hepatic failure secondary to hepatitis A, who was started on continuous venovenous hemodialysis (CVVHD) for acute renal failure. Because anticoagulation with heparin was untenable, regional anticoagulation was accomplished by trisodium citrate (46.7%) infusion. Unfortu- nately, severe hypocalcemia developed when citrate accumulated because of impaired hepatic metabolism. Because of chelation by citrate, the ionized calcium concentration declined to values as low as 2.72 mg/dL (normal, 4.5 to 5.6 mg/dL), whereas the total calcium concentration remained in the normal range. With an unusually high calcium chloride infusion rate via a central line (up to 140 mL/h of 10 mEq/dL CaCl 2 ) and additional boli of CaCl 2 (for a total of 190 mEq), the ionized calcium concentration could be maintained at target levels. Nevertheless, the ionized calcium concentration was maintained in the normal range, and the total calcium concentration increased to a value as high as 15 mg/dL. Thus, the total to ionized calcium ratio was 3.5:1. After 24 hours of treatment, trisodium citrate infusion was gradually reduced from 15 mL/h to 7 mL/h, and the calcium chloride infusion was decreased to 50 mL/h. Nevertheless, persistence of the elevated total to ionized calcium ratio (3:1) indicated citrate accumulation likely secondary to decreased hepatic metabolism. Using this approach, the patient was successfully maintained on CVVHD with regional citrate anticoagulation for a total of 11 days without any additional complications. We conclude that CVVHD with regional citrate anticoagulation can be used in patients with acute hepatic failure if increased CaCl 2 requirements are anticipated and if citrate is infused at a lower rate compatible with decreased citrate metabolism. Citrate accumulation should be suspected in patients with an elevated total to ionized Ca  ratio during CVVHD with citrate anticoagulation.  1999 by the National Kidney Foundation, Inc. INDEX WORDS: Hypocalcemia; continuous venovenous hemodialysis; CVVHD; citrate; regional anticoagulation; liver failure. I T IS WIDELY appreciated that hypocalcemia can occur during the anhepatic phase of liver transplantation. This complication is usually as- sociated with massive transfusion of hemoderi- vates because of accumulation of citrate, the preservative in banked blood. We report a patient with combined acute liver failure and acute renal failure, requiring continuous venovenous hemo- dialysis (CVVHD) with regional citrate antico- agulation as renal replacement therapy. This pa- tient developed acute hypocalcemia evident only by the reduction in the ionized, not the total, fraction. CaCl 2 was required in large amounts to maintain the ionized calcium at the target concen- tration. CASE REPORT A 71-year-old woman, who sought medical attention because of abdominal pain, was found to have profound metabolic acidosis and fulminant hepatic failure secondary to hepatitis A. The patient’s clinical condition worsened rapidly, and she required intubation for acute respiratory distress syndrome. The patient also developed diffuse intra- vascular coagulopathy, sepsis, and acute renal failure. Be- cause of hemodynamic instability, the patient was started on CVVHD as renal replacement therapy. Because heparin was contraindicated, the patient received trisodium citrate 46.7% as regional anticoagulation at a rate of 15 mL/h prefilter and calcium chloride (CaCl 2 , 10 mEq/ dL) at a rate of 30 mL/h through a central line. 1 With this initial approach (see Fig 1 for rate of infusion during initial 24 hours for CaCl 2 and ionized calcium concentrations), the ionized calcium concentration in serum (Ca i ++ ) declined precipitously within 2 hours (from 4.01 mg/dL to 2.72 mg/dL; normal range, 4.5 to 5.6 mg/dL). In an attempt to raise the Ca i ++ concentration to target levels, three ampules of CaCl 2 (one 10-mL ampule of 10% CaCl 2 contains 360 mg From the Division of Renal Disease and Hypertension, The University of Texas Houston, UT-Houston Medical School, Houston, TX 77030. Received September 22, 1998; accepted as submitted November 17, 1998. Address reprint requests to Thomas D. DuBose, Jr., MD, Professor and Director, Division of Renal Disease and Hypertension, The University of Texas Houston, UT- Houston Medical School, 6431 Fannin, MSB 4.148, Hous- ton, TX 77030. E-mail: tdubose@heart.med.uth.tmc.edu  1999 by the National Kidney Foundation, Inc. 1523-6838/99/3304-0038$3.00/0 American Journal of Kidney Diseases, Vol 33, No 4 (April), 1999: E8 1