How To Anticoagulate in Continuous Renal Replacement Therapy

Continuous renal replacement therapy (CRRT) is widely used in the treatment of clinical critical illness. Blood coagulation in extracorporeal circulation is an important problem faced by CRRT. Anticoagulants can prevent blood coagulation in extracorporeal circulation well, but excessive anticoagulation can lead to bleeding. Therefore, ideal anticoagulant measures should be easy to implement and monitor, and have fewer adverse reactions and higher cost-effectiveness.

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The expert group of the Nephrology Branch of the Chinese Medical Association recently published the first edition of the "Guidelines for the Management of Anticoagulation in Continuous Renal Replacement Therapy", making CRRT anticoagulation industry standards to follow.

CRRT anticoagulation assessment and monitoring

The CRRT Anticoagulant Management Guidelines Group gave an opinion: before CRRT, it is recommended that patients should comprehensively evaluate the possible benefits and risks of anticoagulation, and then decide the type and method of anticoagulant use, and dynamically adjust the anticoagulant according to the patient's condition. Adjust the anticoagulation regimen. For patients without active bleeding and coagulation disorders, and not receiving systemic anticoagulant therapy, it is recommended to use anticoagulant drugs during CRRT.

When performing CRRT, regional citrate anticoagulation is recommended instead of heparin, as long as the patient has no contraindications to citrate use. If the patient has a contraindication to the use of citrate and has no risk of bleeding, it is recommended to use unfractionated heparin or low molecular weight heparin instead of other drugs for anticoagulation. This recommendation is in line with the 2012 Kidney Outcomes Improving Global Organization (KDIGO) guidelines for anticoagulation recommendations on CRRT for acute kidney injury. For patients with heparin-related thrombocytopenia (HIT), it is recommended to stop all heparin drugs being used, and it is recommended to use thrombosis inhibitors (such as argatroban or lepirudin) or factor Xa inhibitors (such as danaparin or fondaparinux), rather than other anticoagulants or heparin-free anticoagulants.

Patients with liver cirrhosis or liver failure may consider using regional citrate anticoagulation under close monitoring, and the recommended treatment mode is continuous venovenous hemodialysis (CVVHD) or continuous venovenous hemodiafiltration (CVVHDF).

Local citrate anticoagulation CRRT

In local citrate anticoagulation, two calcium ion concentrations need to be monitored: the calcium ion concentration in extracorporeal circulation can be maintained at 0.25-0.40 mmol/L to achieve a good local anticoagulant effect; the calcium ion concentration in the body is maintained at the normal physiological range of 1.1-1.3 mmol/L.

During local citrate anticoagulation, the serum total calcium level should be monitored at least once a day. If the ratio of serum total calcium to calcium ion is >2.1, the possibility of citrate accumulation should be considered; if the ratio is >2.5, citrate accumulation should be highly suspected. It is recommended to stop using local citrate anticoagulation and switch to other anticoagulation methods. For hyperlactatemia (>4 mmol/L), regional citrate anticoagulation is not recommended. It is recommended to use a bedside rapid blood gas analyzer to detect calcium ion concentration, but attention should be paid to the interference of different blood gas analyzers on the measured value, especially the large difference in the measured value of calcium ion after the filter, and it is necessary to set different targets according to the clinical anticoagulation effect. target value.

Monitor the calcium ion levels in the body after the filter for the first 2 hours, and then perform dynamic monitoring every 6 to 8 hours after stabilization; for patients who are at risk of citrate accumulation, the monitoring interval can be shortened. The blood in the extracorporeal circulation line before the filter can be collected for the determination of pH value and electrolyte concentration; however, when the outlet and inlet ports of the double-lumen catheter are reversely connected to the extracorporeal circulation line, it is recommended to directly collect peripheral blood.

It is recommended to use traditional calcium-free replacement fluid, but calcium-containing replacement fluid can also be used. When local citric acid anticoagulation is used, if the replacement solution prefilled with citric acid is used, it is recommended to use pre-diluted supplementation. It is recommended to use a 4% sodium citrate anticoagulant solution, and ACD-A blood preservation solution can also be used; for blood glucose >10 mmol/L, ACD-A blood preservation solution is not recommended.

It is recommended to use CVVHDF and CVVHD treatment modes. If CVVH is used, the filtration fraction should be controlled from 25% to 30%. When 1.5 mmol/L calcium-containing replacement fluid is used, calcium ion supplementation is still required in the peripheral or extracorporeal circulation circuit, and the initial calcium ion supplementation rate is recommended to be 1.0 mmol/h/L.

Systemic anticoagulation CRRT

When unfractionated heparin is used as an anticoagulant, the recommended initial dose is 2000-3000 IU (30-40 IU/kg), and the maintenance dose is 5-10 IU/kg/h. It is recommended to monitor the activated partial thromboplastin time (APTT), with the goal of maintaining the APTT to 1.2-1.5 times the baseline value or reaching 45-60 s.

When using heparinoids such as danaparin and nadroparin as anticoagulants, the recommended initial dose is 15-25 IU/kg, and the maintenance dose is 5 IU/kg/h. When enoxaparin and other low-molecular-weight heparins are used as anticoagulants, the recommended initial dose is 30-40 IU/kg, and the maintenance dose is 3-5 IU/kg/h. It is recommended to monitor anticoagulant factor Xa activity, with a target value of 0.25-0.35 IU/ml.

When argatroban is used as an anticoagulant, the recommended initial dose is 0.1-0.2 mg/kg/h, and the maintenance dose is 0.1 mg/kg/h. For patients with liver failure, the dose is reduced to 0.05 mg/kg/h. It is recommended to maintain APTT prolongs to 1.2-1.5 times the basic value or reach 45-the 60s.

When nafamostat mesylate is used as an anticoagulant, it can be applied to patients with high bleeding risk. The recommended initial dose is 0.1-0.5 mg/kg, and the maintenance dose is 0.1-0.5 mg/kg/h. It is recommended to maintain the APTT and extend it to the basic 1.2 to 1.5 times the value or reach 45 to 60s.

Anticoagulant-free CRRT

For patients with severe coagulation dysfunction, severe active bleeding, and contraindications to the use of anticoagulants, CRRT without anticoagulants is recommended, but extracorporeal circulation circuits and filter coagulation should be vigilant.

It is recommended to pre-flush the pipeline and filter with heparinized saline, and then flush the pipeline with heparin-free normal saline to prevent systemic heparinization of the patient. When adult patients undergo CRRT without anticoagulants, it is recommended that the blood flow be greater than 200 ml/min on the premise that the vascular access is unobstructed.

It is recommended that the replacement method be pre-dilution, and a combined pre-dilution treatment mode can also be used. During dialysis, it is not recommended to flush the circuit with saline to avoid filter coagulation. Domestic studies have also found that high-frequency saline flushing may not help improve the coagulation function of patients, and may increase the risk of bloodstream infection in extracorporeal circulation

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