Background: Regional citrate anticoagulation (RCA) is not recommended in patients with shock or severe liver failure. We designed a protocol with personalized pre-calculated flow settings for patients with absent citrate metabolism that abrogates risk of citrate toxicity, maintains neutral CKRT circuit calcium mass balance and normal systemic ionized calcium levels. Methods: Single center prospective cohort study of patients in five Adult Intensive Care Units triaged to the CVVHDF-RCA "Shock" protocol. Results: Of 31 patients included in the study, 30 (97%) had acute kidney injury, 16 (52%) had acute liver failure, and 5 (16%) had cirrhosis at the start of CKRT. The median (interquartile range (IQR)) lactate was 5 (3.2 to 10.7), AST 822 (122 to 2950), ALT 352 (41 to 2238), total bilirubin 2.7 (1.0 to 5.1), INR 2 (1.5 to 2.6). The median first hemofilter life censored for causes other than clotting exceeded 70 hours. The cumulative incidence of hypernatremia (Na >148 mM), metabolic alkalosis (HCO3- >30 mM) and hypophosphatemia (P< 2 mg/dL) were 1/26 (4%), 0/30 (0%), 1/30 (3%) respectively and were not clinically significant. Mild hypocalcemia occurred in the first 4 hours in 2/31 patients and corrected by hour 6 with no additional Ca-supplementation beyond the per-protocol administered Ca-infusion. The maximum systemic total Ca (tCa; mM)/ionized Ca (iCa; mM) ratio never exceeded 2.5. Conclusions: The "Shock" protocol can be used without contra-indications and is effective in maintaining circuit patency with a high, fixed ACDA infusion rate to blood flow ratio. Keeping single-pass citrate extraction on the dialyzer >0.75 minimizes the risk of citrate toxicity even in patients with absent citrate metabolism. Pre-calculated, personalized dosing of the initial Ca-infusion rate from a table based on the patient's albumin level and the filter effluent flow rate maintains neutral CKRT circuit calcium mass balance and a normal systemic iCa level.

Background Regional citrate anticoagulation (RCA) for the prevention of clotting of the extracorporeal blood circuit during continuous kidney replacement therapy (CKRT) has been employed in limited fashion because of the complexity and complications associated with certain protocols. Hypertonic citrate infusion to achieve circuit anticoagulation results in variable systemic citrate- and sodium load and increases the risk of citrate accumulation and hypernatremia. The practice of “single starting calcium infusion rate for all patients” puts patients at risk for clinically significant hypocalcemia if filter effluent calcium losses exceed replacement. A fixed citrate to blood flow ratio, personalized effluent and pre-calculated calcium infusion dosing based on tables derived through kinetic analysis enable providers to use continuous veno-venous hemo-diafiltration (CVVHDF)-RCA in patients with liver citrate clearance of at least 6 L/h. Methods This was a single-center prospective observational study conducted in intensive care unit patients triaged to be treated with the novel pre-calculated CVVHDF-RCA “Non-shock” protocol. RCA efficacy outcomes were time to first hemofilter loss and circuit ionized calcium (iCa) levels. Safety outcomes were surrogate of citrate accumulation (TCa/iCa ratio) and the incidence of acid-base and electrolyte complications. Results Of 53 patients included in the study, 31 (59%) had acute kidney injury and 12 (22.6%) had the diagnosis of cirrhosis at the start of CVVHDF-RCA. The median first hemofilter life censored for causes other than clotting exceeded 70 h. The cumulative incidence of hypernatremia (Na > 148 mM), metabolic alkalosis (HCO3- > 30 mM), hypocalcemia (iCa < 0.9 mM) and hypercalcemia (iCa > 1.5 mM) were 1/47 (1%), 0/50 (0%), 1/53 (2%), 1/53 (2%) respectively and were not clinically significant. The median (25th–75th percentile) of the highest TCa/iCa ratio for every 24-h interval on CKRT was 1.99 (1.91–2.13). Conclusions The fixed citrate to blood flow ratio, as opposed to a titration approach, achieves adequate circuit iCa (< 0.4 mm/L) for any hematocrit level and plasma flow. The personalized dosing approach for calcium supplementation based on pre-calculated effluent calcium losses as opposed to the practice of “one starting dose for all” reduces the risk of clinically significant hypocalcemia. The fixed flow settings achieve clinically desirable steady state systemic electrolyte levels.