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      Regional Citrate Anticoagulation Protocol for Patients with Presumed Absent Citrate Metabolism

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          Abstract

          Background

          Regional citrate anticoagulation (RCA) is not recommended in patients with shock or severe liver failure. We designed a protocol with personalized precalculated flow settings for patients with absent citrate metabolism that abrogates risk of citrate toxicity, and maintains neutral continuous KRT (CKRT) circuit calcium mass balance and normal systemic ionized calcium levels.

          Methods

          A 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 AKI, 16 (52%) had acute liver failure, and five (16%) had cirrhosis at the start of CKRT. The median lactate was 5 mmol/L (interquartile range [IQR], 3.2–10.7), AST 822 U/L (IQR, 122–2950), ALT 352 U/L (IQR, 41–2238), total bilirubin 2.7 mg/dl (IQR, 1.0–5.1), and INR two (IQR, 1.5–2.6). 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 one out of 26 (4%), zero out of 30 (0%), and one out of 30 (3%), respectively, and were not clinically significant. Mild hypocalcemia occurred in the first 4 hours in two out of 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 contraindications 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. Precalculated, personalized dosing of the initial Ca-infusion rate from a table on the basis of the patient’s albumin level and the filter effluent flow rate maintains neutral CKRT circuit calcium mass balance and a normal systemic iCa level.

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          Most cited references16

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          Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators.

          Little information is available regarding current practice in continuous renal replacement therapy (CRRT) for the treatment of acute renal failure (ARF) and the possible clinical effect of practice variation. Prospective observational study. A total of 54 intensive care units (ICUs) in 23 countries. A cohort of 1006 ICU patients treated with CRRT for ARF. Collection of demographic, clinical and outcome data. All patients except one were treated with venovenous circuits, most commonly as venovenous hemofiltration (52.8%). Approximately one-third received CRRT without anticoagulation (33.1%). Among patients who received anticoagulation, unfractionated heparin (UFH) was the most common choice (42.9%), followed by sodium citrate (9.9%), nafamostat mesilate (6.1%), and low-molecular-weight heparin (LMWH; 4.4%). Hypotension related to CRRT occurred in 19% of patients and arrhythmias in 4.3%. Bleeding complications occurred in 3.3% of patients. Treatment with LMWH was associated with a higher incidence of bleeding complications (11.4%) compared to UFH (2.3%, p = 0.0083) and citrate (2.0%, p = 0.029). The median dose of CRRT was 20.4 ml/kg/h. Only 11.7% of patients received a dose of > 35 ml/kg/h. Most (85.5%) survivors recovered to dialysis independence at hospital discharge. Hospital mortality was 63.8%. Multivariable analysis showed that no CRRT-related variables (mode, filter material, drug for anticoagulation, and prescribed dose) predicted hospital mortality. This study supports the notion that, worldwide, CRRT practice is quite variable and not aligned with best evidence.
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            Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study.

            To compare the efficacy and safety of adjusted-dose unfractionated heparin with that of regional citrate anticoagulation in intensive care patients treated by continuous venovenous hemofiltration (CVVH). Prospective, randomized, clinical trial in a 32-bed medical and surgical ICU in a university teaching hospital. ICU patients with acute renal failure requiring continuous renal replacement therapy, without cirrhosis, severe coagulopathy, or known sensitivity to heparin. Before the first CVVH run patients were randomized to receive anticoagulation with heparin or trisodium citrate. Patients eligible for another CVVH run received the other study medication in a cross-over fashion until the fourth circuit. Forty-nine circuits (hemofilters) were analyzed: 23 with heparin and 26 with citrate. The median lifetime of hemofilters was 70 h (interquartile range 44-140) with citrate anticoagulation and 40 h (17-48) with heparin (p=0.0007). One major bleeding occurred during heparin anticoagulation and one metabolic alkalosis (pH=7.60) was noted with citrate after a protocol violation. Transfusion rates (units of red cells per day of CVVH) were, respectively, 0.2 (0.0-0.4) with citrate and 1.0 (0.0-2.0) with heparin (p=0.0008). Regional citrate anticoagulation seems superior to heparin for the filter lifetime and transfusion requirements in ICU patients treated by continuous renal replacement therapy.
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              Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients.

              We determined the effect of regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill subjects suffering from acute renal failure who were not at high risk for hemorrhagic complications. Between April 1999 and June 2002, 30 critically ill subjects requiring continuous renal replacement therapy and using 79 hemofilters were randomly assigned to receive regional citrate or systemic heparin anticoagulation. The median hemofilter survival time was 124.5 hours (95% CI 95.3 to 157.4) in the citrate group, which was significantly longer than the 38.3 hours (95% CI 24.8 to 61.9) in the heparin group (P < 0.001). Increasing illness severity score, male gender, and decreasing antithrombin-III levels were independent predictors of an increased relative hazard of hemofilter failure. After adjustment for illness severity, antithrombin-III levels increased significantly more over the period of study in the citrate as compared to the heparin group (P= 0.038). Moreover, after adjustment for antithrombin-III levels and illness severity score, the relative risk of hemorrhage with citrate anticoagulation was significantly lower than that with heparin (relative risk of 0.14; 95% CI 0.02 to 0.96, P= 0.05). Compared with systemic heparin anticoagulation, regional citrate anticoagulation significantly increases hemofilter survival time, and significantly decreases bleeding risk in critically ill patients suffering from acute renal failure and requiring continuous renal replacement therapy.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Kidney360
                Kidney360
                American Society of Nephrology (ASN)
                2641-7650
                February 25 2021
                February 25 2021
                February 25 2021
                December 18 2020
                : 2
                : 2
                : 192-204
                Article
                10.34067/KID.0005342020
                35373034
                6ef32279-0c37-4d28-a355-8fb2240a1023
                © 2020
                History

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