Regional Citrate Anticoagulation for Postdilution Continuous Venovenous Hemofiltration: An Easy Five-Step Prescribing Approach

Xin Xin; Wenxiong Li

doi:10.4103/2665-9190.329043

PERSPECTIVE

Year : 2021 | Volume : 3 | Issue : 1 | Page : 9

Regional Citrate Anticoagulation for Postdilution Continuous Venovenous Hemofiltration: An Easy Five-Step Prescribing Approach

Xin Xin, Wenxiong Li
Surgical Intensive Care Unit, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

Date of Submission	08-Aug-2021
Date of Acceptance	03-Sep-2021
Date of Web Publication	22-Oct-2021

Correspondence Address:
Prof. Wenxiong Li
Surgical Intensive Care Unit, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing - 100020
China

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2665-9190.329043

Abstract

Regional citrate anticoagulation (RCA) is the preferred anticoagulation method of continuous renal replacement therapy (CRRT) which is recommended by international guidelines, but the use of citrate anticoagulation is relatively complicated. If correct prescription and timely adjustment of RCA are not performed, disorders of fluid electrolyte and acid-base balance are prone to occur, especially hypocalcemia, which is a fatal complication. This article introduces the use of RCA with calcium-containing replacement fluid for postdilution continuous veno-venous hemofiltration, which provides a simple and easy CRRT anticoagulation protocol for clinical practice.

Keywords: Continuous renal replacement therapy, regional citrate anticoagulation, prescription

How to cite this article:
Xin X, Li W. Regional Citrate Anticoagulation for Postdilution Continuous Venovenous Hemofiltration: An Easy Five-Step Prescribing Approach. J Transl Crit Care Med 2021;3:9

How to cite this URL:
Xin X, Li W. Regional Citrate Anticoagulation for Postdilution Continuous Venovenous Hemofiltration: An Easy Five-Step Prescribing Approach. J Transl Crit Care Med [serial online] 2021 [cited 2023 Mar 31];3:9. Available from: http://www.tccmjournal.com/text.asp?2021/3/1/9/329043

Introduction

In comparison to systemic heparin anticoagulation, regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) not only reduces the risk of bleeding complication but also provides a longer filter lifespan.^[1],[2] Considering these advantages, it is recommended in the kidney disease: improving Global Outcomes (KDIGO) clinical practice guideline for patients who require CRRT and without contraindications for RCA.^[3] The common modalities for CRRT are continuous venovenous hemodiafiltration, continuous venovenous hemodialysis, and continuous venovenous hemofiltration (CVVH), in which the CVVH is an easy-operated and classical CRRT modality.^[4] Patients who undergo RCA for CRRT have a higher risk of hypocalcemia,^[2] and only calcium-containing replacement fluid is commercially available in China. Theoretically, calcium-containing replacement fluid is recommended only for postdilution CVVH in theory, and commercially available products could make clinical work more effective.^[4] Hence, RCA for postdilution CVVH is widely used in clinical practice. Here, we describe a five-step approach to prescribe this protocol. Moreover, a flow chart shows the prescribing approach for RCA [Figure 1].

Figure 1: Flow chart of the five-step prescribing approach for regional citrate anticoagulation

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The first step: Counting the initial infusion rate of the citrate solution in terms of blood flow rate in the extracorporeal circuit.

The initial infusion rate of 4% trisodium citrate (commercially available product in China) is determined by the target blood citrate level (3–5 mmol/L) in the extracorporeal circuit [Figure 2].^[4] The molecular weight of trisodium citrate is 294 g/mol, and the molar concentration of 4% trisodium citrate is 136 mmol/L.^[5] If the blood flow rate is 150 ml/min (9000 ml/h), supposing an initial infusion rate of 4% trisodium citrate is X (ml/h), and the target blood citrate level in the extracorporeal circuit is 4 mmol/L, then a formula could be built as follows:

Figure 2: The schematic diagram of postdilution continuous venovenous hemofiltration with regional citrate anticoagulation

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(136 mmol/L × X)/9000 = 4 mmol/L

X = 265 ml/h

As the blood flow rate changes, the infusion rate of the citrate solution changes accordingly [Table 1].

Table 1: Blood flow rate and matched citrate infusion rate by the target blood citrate level of 4 mmol/L in the filter

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In summary, if the blood flow rate is set at Y (ml/min) and the target blood citrate concentration is C (mmol/L) in the filter, and X (ml/h) is the initial infusion rate of 4% trisodium citrate, then the formula is as follows:

136X/60Y = C

X = 0.44 × C × Y (ml/h)

The second step: Adjusting the infusion rate of the citrate solution in terms of the postfilter ionized calcium concentration monitoring.

After the initial citrate infusion rate is determined, the adjustment of citrate infusion rate depends on the serum ionized calcium concentration in the postfilter. During CRRT, postfilter ionized calcium level is recommended to maintain at 0.25–0.35 mmol/L [Figure 2].^[6],[7],[8] The first measurement is suggested at 30 or 60 min after the start of CRRT with RCA. A study showed that systemic citrate concentration, ionized calcium levels, and the rate of calcium supplementation were substantially variable within the first 2–4 h of RCA.^[9] Thus, postfilter ionized calcium levels should be monitored hourly within the first 4 h of RCA, and the citrate infusion rate should be adjusted according to the monitored results [Table 2]. If the postfilter ionized calcium level is in the range of 0.25–0.35 mmol/L, we suggest monitoring the postfilter ionized calcium level every 4 h; if the postfilter ionized calcium level is not in this range, the infusion rate of 4% trisodium citrate needs to be adjusted [Table 2], and the postfilter ionized calcium level should be repeated within 1 h after each adjustment.^[10]

Table 2: Adjustment of citrate infusion rate in terms of postfilter ionized calcium concentration monitoring

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If the serum ionized calcium concentration in the postfilter does not reach the target of anticoagulation, increasing the citrate infusion rate and/or decreasing the blood flow rate in the extracorporeal circuit could be considered, which can both reduce serum ionized calcium concentration in the filter and ensure the target postfilter ionized calcium concentration appropriately.^[6],[11]

The third step: Setting the initial infusion rate of calcium solution in terms of calcium loss rate by CVVH.

During RCA, calcium supplementation is required to maintain systemic serum ionized calcium in the range of 1.1–1.3 mmol/L [Figure 2]. Serum calcium exists in 3 forms: 40%–45% protein-bound calcium, 50% ionized calcium, and 5%–10% complexed calcium^[12] [Figure 3]. Ionized calcium and complexed calcium could be cleared by CVVH. Citrate chelates ionized calcium to form citrate-calcium complex, which could be dissociated quickly in the body, and released ionized calcium. Therefore, in the absence of citrate accumulation, calcium supplementation for the chelated calcium is unnecessary. However, because of a shift of calcium ions from protein binding to citrate complexes in the extracorporeal circuit, which changes the proportion of calcium components, the calcium loss rate by CVVH during RCA is higher than heparin anticoagulation, and higher systemic calcium supplementation is required.^[13]

Figure 3: The serum calcium components

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Our study showed that the calcium infusion rate correlated significantly with the calcium loss rate by CVVH.^[10] The ultrafiltrate total calcium (1.87 ± 0.18 mmol/L) was higher than the systemic ionized calcium (1.08 ± 0.11 mmol/L) but lower than the systemic total calcium (2.13 ± 0.24 mmol/L). Simultaneously, the ultrafiltrate ionized calcium (0.47 ± 0.10 mmol/L) was significantly lower than the systemic ionized calcium, which indicated that CVVH removes calcium mainly in the form of citrate-calcium complex. Therefore, the rate of calcium supplementation is primarily related to the removal of calcium by CVVH, and the higher ultrafiltration rate (UFR), the more calcium is removed by CVVH. In addition, a small amount of calcium is excreted in urine and feces. Furthermore, the initial calcium supplementation formula is summarized as follows:^[10]

Calcium infusion rate (mmol/h) = 1.77 + 0.8× (calcium loss rate by CVVH, mmol/h).

The hourly calcium loss rate by CVVH is the product of UFR (L/h) and measured ultrafiltrate total calcium concentration (mmol/L).

Our previous study also showed that postdilution CVVH was performed with a fixed blood flow rate of 150 ml/min and replacement fluid flow rate of 2000 ml/h for each new circuit, the infusion rate of 4% trisodium citrate in the prefilter was 220 ml/h (30 mmol/h), then the net ultrafiltration is about 500 ml/h which was adjusted according to the clinical status, and the initial infusion rate of 10% calcium gluconate postfilter was set at about 25 ml/h (5.5 mmol/h).^[10] If a calcium-containing replacement fluid is used for postdilution CVVH, an additional calcium supplement is still needed. When we use the commercially available replacement fluid product (Qingshan, Chengdu), which is a calcium-containing replacement fluid (10.6 mmol/L glucose, 118 mmol/L Cl^-, 0.797 mmol/L Mg²⁺, 1.60 mmol/L Ca²⁺, and 113 mmol/L Na⁺), then an additional calcium supplement rate could be 5.5 – (1.6 × 2) = 2.3 (mmol/h), which is equivalent to 10 ml/h of 10% calcium gluconate approximately.

Ten percent calcium gluconate and 10% calcium chloride are commonly used in clinical practice in China. 10% calcium gluconate contains 0.22 mmol of ionized calcium per ml, and 10% calcium chloride contains 0.68 mmol of ionized calcium per ml.^[13] Calcium is recommended to infuse into the systemic circulation through a separate line rather than the venous return line due to the increased risk of clotting of the extracorporeal circuit. Calcium chloride should be infused through central line due to its sclerosing effect on peripheral veins; calcium gluconate can be delivered through any venous access.^[5] In addition, chloride ions increase the risk of acid-base disorders. Thus, clinicians tend to use 10% calcium gluconate more frequently.

The fourth step: Adjusting the infusion rate of supplemental calcium in terms of the systemic ionized calcium concentration monitoring.

The first monitoring of systemic ionized calcium is suggested at 30 or 60 min after the start of RCA [Figure 2]. Systemic ionized calcium levels should be monitored hourly within the first 4 h of RCA, and the infusion rate of 10% calcium gluconate should be adjusted according to the monitored results. If the systemic ionized calcium level is normal (1.1–1.3 mmol/L), it is recommended to repeat the monitoring every 4 h; if the systemic ionized calcium level is abnormal, then adjust the infusion rate of 10% calcium gluconate according to [Table 3] and repeat it within 1 h until the systemic ionized calcium level return to normal.^[14]

Table 3: Adjustment of 10% calcium gluconate infusion rate in terms of the systemic ionized calcium concentration monitoring

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The fifth step: Adjusting the infusion rate of sodium bicarbonate in terms of the pH and HCO₃^- monitoring.

The replacement fluid contains two components, which are A and B fluids. A fluid (Qingshan, Chengdu) is the commercially available product and B fluid is sodium bicarbonate (5% NaHCO₃) in China. During CVVH with RCA, since sodium bicarbonate could be cleared through the filter, the replacement solution should contain sodium bicarbonate, and the HCO₃^- concentration is usually in the range of 30–35 mmol/L in the replacement fluid.^[14] 1 mmol of trisodium citrate is metabolized to 1 mmol of citric acid (C₆H₈O₇) and 3 mmol of NaHCO₃ upper.^[5] Therefore, trisodium citrate could be regarded as B fluid to a certain extent. However, bicarbonate produced by citrate metabolism is usually not enough to meet the metabolic needs of the body. Thus, an additional infusion of 5% NaHCO₃ is still required during RCA, but the sodium bicarbonate supplemental dose is significantly less than heparin anticoagulation. In particular, it is essential to monitor pH, HCO₃^- and Na⁺ by blood gas and electrolyte analysis to adjust the infusion rate of 5% NaHCO₃ and maintain electrolyte and acid-base balance. Especially, physicians should avoid hyponatremia, hypernatremia, and citrate accumulation during RCA.

Since calcium-containing replacement fluid (A fluid) is the only commercially available product in China, postdilution CVVH with RCA is a reasonable protocol when calcium-containing replacement fluid is used. When setting the CRRT parameters for postdilution CVVH with RCA, we should also take the filter lifespan issue into consideration and control filter fraction below 25%–30%.^[15]

The above is an easy five-step approach we proposed, and these steps do not follow a chronological sequence. We believe that it could be helpful for physicians to prescribe postdilution CVVH with RCA.

Financial support and sponsorship

This study is supported by Beijing Municipal Science and Technology Commission (grant No. Z191100006619032).

Conflicts of interest

There are no conflicts of interest.

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