The application of CRRT is no longer limited to replacement therapy for patients with renal insufficiency but has also been extended to the treatment of critically ill patients with severe sepsis, severe trauma, burns, severe acute pancreatitis etc., and has played an irreplaceable role in reducing mortality in critically ill patients [9, 10–11]. This method requires drawing blood from the patient. Moreover, the treatment duration is long, and coagulation in the tubing and filter reduces the service life of the filter, resulting in treatment interruption, increased treatment costs, increased health care workload, and blood loss of patients [12–13]. Therefore, anticoagulation is a key component to ensure the smooth performance of CRRT. However, this requirement can be a challenge, as many critically ill patients are at increased risk of bleeding.
The safety and efficacy of anticoagulation in CRRT have been the focus of clinical researchers.
The application of local citrate anticoagulation in CRRT for critically ill patients has received much attention in recent years because of its unique advantages.
The principle of citrate anticoagulation is mainly to affect the level of ionised calcium in blood and thus intervene in the coagulation process [14
]. After pumping citrate through the arterial end of the CRRT tubing, the ionised calcium in blood binds to citrate radical to form calcium citrate, so that the ionised calcium concentration in extracorporeal blood is reduced and the conversion of prothrombin to thrombin is affected. It also affects other coagulation links, thus maintaining the post-filter calcium ion concentration at 0.25–0.35 mmol/L for optimal anticoagulation effect in the extracorporeal circulation [5
]. After entering the body, citrate group participates in the tricarboxylic acid cycle in the liver, muscle tissue and renal cortex, and is quickly metabolised to bicarbonate radical ions without any residue[4
]. Supplementation with sufficient ionised calcium to maintain its blood concentration at 1.00–1.20 mmol/L before the blood returns to the body through the venous end will restore the coagulation process in the body to normal. As a result, there will be no systemic anticoagulant effects, which in turn can reduce the incidence of bleeding complications [5
], and avoid the adverse effects associated with low calcium. Previous studies have confirmed that citrate is safe and effective for haemodialysis in patients with a high-risk of bleeding [6
]. Local citrate anticoagulation was also reported to prolong the duration of CRRT and reduce the cost of treatment [20
There are two main infusion methods commonly used when citrate is applied for anticoagulation in CRRT: one is priming citrate anticoagulation, in which citrate is added to the replacement fluid so that it becomes a part of the replacement fluid . The advantage of this method is that electrolyte disturbances are less likely to occur, although it is not suitable for precise adjustment. The other mode is synchronous local citrate anticoagulation , in which citrate is infused separately from the replacement fluid and the infusion rate of citrate is adjusted according to the monitored ionised calcium and acid-base concentrations. The advantage of this method is that the infusion rate of citrate can be adjusted in real time, thus achieving a better anticoagulation effect. In clinical implementation, citrate is pumped from the outlet end of CRRT via a separate infusion pump. There are clinical situations where the actual infusion rate of the infusion pump is not consistent with the intended infusion rate, which may result in variations in the actual amount of citrate administered over a certain period of time. Reduced citrate concentration will lead to inadequate anticoagulation, tubing coagulation, reduced treatment time, acidosis etc. whereas increased citrate levels can lead to a subsequent risk of citrate accumulation, alkalosis etc. We have implemented a modified citrate infusion method in clinical practice by placing the citrate solution directly in the original position with 5% sodium bicarbonate on the CRRT machine, setting the pump speed of the machine(Grouping and treatment protocols), and administering it when the blood is just drawn out of the body, which is closer to the outlet end than the conventional infusion position. This can result in effective calcium chelation in blood reducing the risk of coagulation, and allowing for longer treatment duration and lower transmembrane pressure at the time of disconnection from CRRT circuit. We further inferred that the modified citrate infusion method can stabilise the citrate infusion rate, reduce problems associated with unstable citrate infusion rates, and allow more adequate chelation of blood calcium. We therefore monitored venous end ionised calcium levels of patients. The levels were found to be closer to the values required for anticoagulation with minimum fluctuations. A higher level of ionised calcium at the venous end and a greater range of fluctuations imply an increased chance of coagulation.
The major complications of citrate anticoagulation include citrate accumulation, hypocalcaemia, hypernatraemia and metabolic acid-base disorders . Citrate affects systemic coagulation, and there have been few reports of bleeding induced by citrate anticoagulation . The ideal state of anticoagulation in CRRT is to achieve a good anticoagulation effect without associated complications. We included 60 treatment sessions in each of the study groups and none of the patients had hypocalcaemia or hypernatraemia, due to close monitoring and adjustment during our treatment. The occurrence of citrate accumulation is related to various factors such as the patient's hepatic function, shock, as well as the infusion rate and dose of citrate . Citrate accumulation was not observed in the patients of modified infusion group, while three episodes of citrate accumulation occurred in the conventional infusion group. Although the difference in incidences of citrate accumulation between the two groups was not statistically significant, the values were marginally lower in the modified infusion group. This can be related to accurate infusion rate of citrate in the modified infusion group. In addition, the total calcium monitored after treatment was higher in the conventional infusion group, and the elevated total calcium may mean a greater possibility of citrate accumulation. There was no statistically significant difference in acid-base status, coagulation, or hepatic function indicators between the two groups after treatment.
We currently use citrate (3% sodium citrate) as a blood-preserving solution. Due to the immediate anticoagulant effect of citrate, in the conventional way of local citrate infusion, nurses have to change the citrate infusion bag about once every 2 h. But with high clinical workload, increased number of critically ill patients, and heavy workload on nurses, frequent changing of infusion bag undoubtedly poses a challenge . Absence of citrate infusion due to delay in changing of the infusion bag can increase the risk of coagulation. Moreover, while infusing citrate in the conventional way, nurses have to include the amount of citrate in the calculation of fluid volume, which also increases the clinical workload of nurses and causes difficulties in fluid management. In contrast, the modified local citrate infusion method adds citrate to a three-litre bag, which is placed on a scale same as the CRRT replacement fluid. The number of infusion bag replacements and hence time without citrate-free infusion is reduced. It also avoids inclusion of citrate volume in the fluid volume calculations, thus reducing the difficulty in fluid management. Nurses changed the citrate infusion bags much less frequently for the patients in the modified citrate compared to those in conventional group, and the differences between the two groups was statistically significant.
Thus, the modified local citrate infusion method improves filter service life, prolongs treatment duration, achieves a significantly better anticoagulant effect than conventional citrate infusion, has a lower risk of citrate accumulation, does not increase metabolic complications, reduces the burden of nursing operations, and increases patient safety.