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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2015  |  Volume : 26  |  Issue : 4  |  Page : 739-742
Hemodiafiltration using pre-dilutional on-line citrate dialysate: A new technique for regional citrate anticoagulation: A feasibility study


1 Department of Anesthesia and Critical Care, Military Hospital of Tunis, Faculty of Medicine, Tunis, Tunisia
2 Department of Extra-renal Blood Purification, Military Hospital of Tunis, Faculty of Medicine, Tunis, Tunisia

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Date of Web Publication8-Jul-2015
 

   Abstract 

A prospective, observational, feasibility study was carried out on four patients with end-stage renal failure undergoing bicarbonate hemodialysis to study the feasibility of an on-line hemodiafiltration technique using a citrate dialysate with pre-dilutional infusion of citrate as a technique for regional citrate anticoagulation. All patients had contraindication to systemic heparin anticoagulation. The dialysis technique consisted of an on-line hemodiafiltration with a citrate dialysate without calcium using a Fresenius 4008S dialysis machine and Fresenius Polysulfone F60 dialyzers. The infusion solution was procured directly from the dialysate and was infused into the arterial line. To avoid the risk of hypocalcemia, calcium gluconate was infused to the venous return line. The study was carried out in two stages. During the first stage, the citrate infusion rate was 80 mL/min and the calcium infusion rate was 9 mmol/h. At the second stage, the rates were 100 mL/min and 11 mmol/h, respectively. The primary endpoint of this study was the incidence of thrombosis in the extracorporeal blood circuit and/or the dialyzer. A total of 78 sessions were conducted. All the sessions were well tolerated clinically and there were no major incidents in any of the four patients. At the first stage of the study, there were five incidences of small clots in the venous blood chamber, an incidence of extracorporeal blood circuit thrombosis of 12.5%. At the second stage of the study, no cases of extracorporeal blood circuit or dialyzer thrombosis were noted. Hemodiafiltration with on-line citrate dialysate infusion to the arterial line is safe and allows an effective regional anticoagulation of the extracorporeal blood circuit without the need for systemic anticoagulation.

How to cite this article:
Bousselmi R, Baffoun A, Hajjej Z, Saleh MB, Labbene I, Ferjani M, Hmida MJ. Hemodiafiltration using pre-dilutional on-line citrate dialysate: A new technique for regional citrate anticoagulation: A feasibility study. Saudi J Kidney Dis Transpl 2015;26:739-42

How to cite this URL:
Bousselmi R, Baffoun A, Hajjej Z, Saleh MB, Labbene I, Ferjani M, Hmida MJ. Hemodiafiltration using pre-dilutional on-line citrate dialysate: A new technique for regional citrate anticoagulation: A feasibility study. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2019 Jul 23];26:739-42. Available from: http://www.sjkdt.org/text.asp?2015/26/4/739/160195

   Introduction Top


Extracorporeal blood circuit anticoagulation is mandatory to prevent thrombosis during hemodialysis (HD). Heparin is the most used anti-coagulant agent. There are several alternatives for those cases with contraindication or allergy to heparin. These include the use of lepirudin, danaparoid, prostacyclin, nafamostat mesilate and citrate. Regional citrate anticoagulation (RCA) is an effective alternative to prevent thrombosis of the extracorporeal blood circuit in HD patients at high risk of bleeding and in those with heparin-induced thrombocytopenia. It was first described in 1961 by Morita. [1] RCA techniques described in the literature are based either on the use of a citrate dialysate or on the use of trisodium citrate infusion on the arterial line. The first has the disadvantage of the lack of anticoagulation of the arterial line with a substantial risk of thrombosis. [2] The second uses sterile solutions of trisodium citrate, which are not always available. In this work, we studied the feasibility of an on-line infusion of citrate dialysate, directly procured from the dialysate, to the arterial line.


   Methods Top


In this prospective, feasibility study, four patients with end-stage renal disease (ESRD) regular HD consented to be included. In all these patients, the use of heparin for systemic anticoagulation was contraindicated. The first patient aged 23 years with idiopathic renal failure was on conventional bicarbonate HD using heparin for extracorporeal circuit anti-coagulation, but he soon developed a heparin-induced thrombocytopenia. The second patient aged 63 years with diabetic nephropathy developed persistent gastrointestinal bleeding due to jejunal angiodysplasia not accessible to endoscopic therapy and exacerbated by the use of heparin during HD sessions. The remaining two patients aged 47 and 60 years, with recently diagnosed idiopathic ESRD requiring HD, presented with pericardial effusion, a contraindication for the use of heparin during dialysis.

The dialysis technique consisted of an on-line hemodiafiltration using a citrate dialysate without calcium. We used the Fresenius 4008S dialysis machine and Fresenius polysulfone F60 dialyzers in all patients. The dialysate composition is given in [Table 1]. The citrate infusion solution was taken directly from the dialysate and was infused to the arterial line. To avoid the risk of blood contamination with endotoxin from the dialysate, two Fresenius Diasafe anti-bacterial filters were placed in the line. To avoid the risk of hypocalcemia, calcium gluconate was infused to the venous return line.
Table 1: Dialysate composition.

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The study was carried out in two stages. During the first stage, we used the following parameters: Blood flow rate of 300 mL/min, dialysate flow rate of 500 mL/min, citrate infusion rate of 80 mL/min, calcium infusion rate of 9 mmol/h and bicarbonate dialysate concentration of 34 mmol/L. At the second stage, the parameters were: Blood flow rate of 400 mL/min, dialysate flow rate of 500 mL/ min, citrate re-injection flow rate of 100 mL/ min, calcium infusion rate of 11 mmol/h and bicarbonate dialysate concentration of 38 mmol/L. For both the stages, the duration of the sessions was set at 4 h and the ultrafiltration rate was set depending on the desired loss of weight, but always under 10 mL/kg/h.

Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored every 15 min during the sessions. Signs of poor clinical tolerance, such as headaches, nausea and vomiting, as well as clinical signs of hypocalcemia, such as muscle cramps, paresthesia or seizures, were also continuously monitored. Blood was sampled for ionized calcium concentration from the arterial and venous lines every 30 min using a blood gas analyzer (Stat Profile pHOx Plus C; Nova Biomedical Corporation, Waltham, MA, USA). The blood pH was assessed at T 0 (before beginning the session), T 2 (at the middle of the session) and T4 (at the end of the session) using the same blood gas analyzer. Sodium, potassium, chloride, bicarbonate, phosphorus, total calcium, magnesium and urea were also tested at T0 , T2 and T4 .

The extracorporeal blood circuit and the dialyzer were examined at the end of each session to determine if there was thrombosis in them. This examination was performed by the same experienced nurse for all the sessions. The primary endpoint of this study was the incidence of thrombosis on the extracorporeal blood circuit and the dialyser. The secondary endpoints were the clinical tolerance of the technique, the quality of diafiltration measured by the urea reduction ratio (URR), the incidence of hypocalcemia and the incidence of electrolyte and acid-base disorders.


   Results Top


A total of 78 sessions were conducted. Forty sessions were performed with the first-stage parameters and 38 sessions with the secondstage parameters. All the sessions were well tolerated clinically and we did not observe any major incidents in any of the four patients [Table 2].
Table 2: Clinical tolerance.

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All the sessions were conducted for 4 h and we never had to interrupt sessions due to xtracorporeal blood circuit or dialyzer thrombosis. At the first stage of the study, there were only five episodes of small clots in the venous chamber, an incidence of 12.5% of extracorporeal blood circuit or dialyzer thrombosis. The second stage of the study had no cases with blood clots. The mean ionized calcium concentration at the arterial line was 0.44 ± 0.08 mmol/L at the first stage of the study and 0.37 ± 0.04 mmol/L at the second stage [Table 3].
Table 3: Extracorporeal blood circuit anticoagulation.

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The mean URR was 54 ± 7% at the first stage of the study and 66 ± 9% at the second stage. Nine cases of mild hypocalcemia, but without any clinical signs, were noted at the end of the session at the first stage of the study. At the second stage, only one case of hypocalcemia with muscle cramps was noted. A poor correction of the metabolic acidosis at the end of the session was noted in 30% of the cases at the first stage of the study. No cases of persistent metabolic acidosis were noted at the second stage of the study [Table 4].
Table 4: URR, calcium levels and acid–base disorders.

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   Discussion Top


The principle of RCA is to chelate calcium throughout the extracorporeal blood circuit and then prevent thrombosis. An ionized calcium concentration below 0.4 mmol/L is required to effectively prevent thrombosis. [3] Classically, trisodium citrate infusion to the arterial line or citrate dialysate was used to perform RCA for intermittent HD. But, sterile trisodium citrate for intravenous infusion is not always available and the use of a citrate dialysate is associated with a substantial risk of thrombosis as the arterial line of the extracorporeal blood circuit is not anticoagulated. [2] In this study, we investigated the feasibility of a new regional citrate anticoagulation technique for intermittent HD. We used an on-line infusion of pre-dilutional citrate dialysate. We were able to totally prevent thrombosis in the extra-corporeal blood circuit and the dialyzer with a citrate infusion rate of 100 mL/min. This rate of citrate infusion allowed us to have an ionized calcium concentration of 0.37 mmol/L in the extracorporeal blood circuit. The clinical tolerance of this technique was good for all the patients, throughout the 78 sessions. The quality of purification was improved keeping a blood flow rate of 400 mL/ min without having any adverse effect on the hemodynamics or the patients' tolerance. The occurrence of hypocalcemia was effectively avoided using an infusion of calcium on the venous return line at a rate of 11 mmol/h. The tendency for metabolic acidosis, which was noted at the first stage of the study, was subsequently avoided by adjusting the bicarbonate concentration of the dialysate.

A Medline search for on-line infusion of citrate dialysate during hemodiafiltration found only one clinical trial. [4] In this trial, the authors used a post-dilution on-line infusion of citrate dialysate and they were able to totally avoid heparin. They concluded that post-dilution online infusion of citrate dialysate is safe and effective in patients with a high risk of bleeding.

In our study, we chose undiluted citrate infusion to optimize the anticoagulation of the arterial line and the dialyzer. We were able to totally prevent extracorporeal blood circuit thrombosis without the risk of systemic anticoagulation. In fact, the infusion of calcium at the venous line restored a normal ionized calcium concentration and thus a normal coagulation profile as well.

Using an undiluted on-line infusion of citrate dialysate for hemodiafiltration is safe and allows for an effective regional anticoagulation of the extracorporeal blood circuit without the need for systemic anticoagulation. Our trial is the first to find these encouraging results. Further studies are needed to confirm the effectiveness of this technique.


   Acknowledgments Top


The authors are grateful to the patients and all the team of the Department of Hemodialysis of the Military Hospital of Tunis.

Conflict of interest: The authors declare no conflict of interest.

 
   References Top

1.
Morita Y, Johnson RW, Dorn RE, Hall DS. Regional anticoagulation during hemodialysis using citrate. Am J Med Sci 1961;242:32-43.  Back to cited text no. 1
[PUBMED]    
2.
Stegmayr BG, Jonsson P, Mahmood D. A significant proportion of patients treated with citrate containing dialysate need additional anticoagulation. Int J Artif Organs 2013;36:1-6.  Back to cited text no. 2
    
3.
Falkenhagen DT, Brandi M. Correlation between Activated Clotting Time and Ionized Calcium in Regular Dialysis Treatment Patients (Poster). EDTA; 2011.  Back to cited text no. 3
    
4.
J, Petitclerc T, Créput C. Safe use of citric acid-based dialysate and heparin removal in post dilution online hemodiafiltration. Blood Purif 2012;34:336-43.  Back to cited text no. 4
    

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Correspondence Address:
Radhouane Bousselmi
Department of Anesthesia and Critical Care, Military Hospital of Tunis, Faculty of Medicine, Tunis
Tunisia
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DOI: 10.4103/1319-2442.160195

PMID: 26178547

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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