Material and Methods
- 1.
Study design
This is a retrospective single-center study performed in a teaching hospital-based dialysis unit (Lapeyronie Hospital, Montpellier, France) using data extracted from patient electronic dialysis medical records. Data collection extended from October 1, 2009, to May 31, 2012 (30 months of follow-up). All data collected were part of clinical dialysis performances and quality control assessment precisely protocolized and performed monthly (first week of the month, midweek session).
The study consisted of two parts: firstly, a baseline assessment of clinical performances corresponding to a cross-sectional analysis using data of three consecutive months while patients being clustered by vascular access type (tunneled CVC, AVA); secondly, a longitudinal follow-up of clinical performances up to 30 months while patients were clustered by vascular access type.
Clinical dialysis performance indicators consisted of effective blood flow, access recirculation, urea spKt/V and dpKt/V (Daugirdas), ionic dialysance measurement (Online Clearance Measurement, OCM) from dialysis machine (OCMKt/V), total clearance delivered per session (Kt), total ultrafiltration volume (VUF) and substitution volume (VSUB) per session, albumin, Hemoglobin.
- 2.
Patients
This study enrolled 68 stage 5 chronic kidney disease dialysis dependent patients (CKD5D) receiving high volume hemodiafiltration. Ten were incident patients (< 3 months treatment) and 58 were prevalent patients (≥3 months treatment). Some incident patients were converted during the study to arteriovenous fistula or graft access.
- 3.
Ethics statement
The study was conducted according to the principles of the Declaration of Helsinki and in compliance with International Conference on Harmonization/Good Clinical Practice regulations. According to the French Law, the study has been registered at “Ministère de la Santé et des Solidarités” after approval by the Montpellier University Hospital’s ethics committee (Comité de Protection des Personnes Sud Méditerranée IV) with the following number DC-2008-417. All patients gave their written informed consent.
- 4.
Vascular accesses
DualCath (DCath) is manufactured by MedComp in USA and distributed in Europe 23-26. DCath consists of two independent single lumen silicon catheters and their tubing extension adaptor are presented separately, with all material required for insertion (2 single lumen silicone cannula with their semi-rigid plastic stylets, straight tunneler, syringes, needle, sutures, large bore needles, two wire guides 50 cm, two external adaptors, two introducer-dilator catheters), packaged in a sterile tray protected by a double transparent plastic film.
DCath consists of two single lumen silicone cannulas with separate tubing extension adaptors that are docked together at the time of insertion. They present circular mark every 5 cm to precisely know length of the catheter. The intravascular cannula is made of radiopaque silicone polymer tubing (length 40 cm, inner/outer diameters 2.0/3.2 mm). The length of cannulas is adjusted at the time of insertion to patient anthropometry. As such, DCath may differ according to patient height and side of insertion: 25–27 cm and 30–32 cm for the right and left sides respectively. Six holes are disposed spirally along their distal tip. The extension or adaptor is made of 6-7 cm silicone polymer of larger diameter ending in a nylon luer-lock connection device with colored marks (blue, venous; red, artery).
- 4.1.
DualCath Insertion
DCath insertion relies on a percutaneous method performed under local anesthesia by trained nephrologist in a clean room or theater with support of a nurse and appropriate environment and material (bed, resuscitation, light, medication, gas). Most of DCath insertions were performed under local anesthesia, sometimes with support of nitrogen dioxide gas under mask, rarely DCath insertion required general anesthesia (complex case, anxiety). Patient preparation consisted of skin washing, nonabrasive shaving and iodine disinfection (betadine) 1 hour before DCath insertion.
Choice of the central vein location depends on the anatomical condition of the patient. Vast majority of patients had DCath inserted in the right internal jugular vein, few had insertion in the left internal jugular or femoral vein as alternative options. For practical reason, vein cannulation was mainly based on landmark technique rather than guided by US mapping. Vein US mapping was mostly applied in complex cases. During the preparation of catheter insertion, landmarking of skin area and vein location was performed and drawn on skin with surgical skin marker.
Vein cannulation was performed using strictly aseptic surgical conditions, including mask, hat, sterile gown and gloves for the operator and sterile drapes covering most of patient body and leaving access to the region of interest.
DCath insertion consists usually in five main steps. In the case of right internal jugular vein cannulation, a brief description of the different steps is given here:
The first step consists of local anesthesia in the prethoracic area and at the base of the neck region at the top of the Sedillot triangle.
The second step consists in locating the right internal jugular vein and inserting the two silastic cannulas into the right internal jugular vein based on a percutaneous-based method using a desilet technique relying on an introducer and a vein dilator.
The third step consists of tunnelling each cannula with a metallic tunneler advanced in the subcutaneous tissue through the cervical hole downward following the anesthetized track and exiting in the prethoracic area. Cannula is firmly attached to the tunneler with a tressed nylon suture which is then passed through tunnel with cannula. The second cannula is tunneled with the same method in a parallel subcutaneous track.
The fourth step consists in shortening the cannulas to fit chest patient size with use of space band marks, putting on a silicone rubber collar, and then docking the external extension piece ending by luer-lock connector to the cannula. Cannula and tubing extension assembly are then rigidified by plastic stylet and pushed back with a twisting movement through the enlarged skin exit. Cannulas are then rinsed with saline and clamped with a vascular atraumatic clamp. Anchoring the two cannulas together is then performed with a subcutaneous nylon suture through the jugular neck hole. The two threads emerging from the cervical cutaneous orifice are recovered, isolated, and firmly tied together to create a bridge suture between the two cannulas (stays).
The fifth step consists in closing skin cutaneous orifice with intradermal sutures, rinsing, locking cannulas with antithrombotic solution and capping them with Luer-lock caps.
- 4.2.
Figure 1 presents a cartoon of the DCath inserted in the right internal jugular vein with a picture of the skin exit looking. Chest X-Ray is performed before catheter use to secure catheter position and check the lack of abnormalities or complications.
Figure 1.
Cartoon of the DCath inserted in the right internal jugular vein with a picture of the skin exit looking. Chest X-Ray is performed before catheter use to secure catheter position and check the lack of abnormalities or complications.
Figure 1.
Cartoon of the DCath inserted in the right internal jugular vein with a picture of the skin exit looking. Chest X-Ray is performed before catheter use to secure catheter position and check the lack of abnormalities or complications.
- 4.3.
DualCath Management and Handling
DCath are used exclusively for hemodialysis purpose and any other use (i.e., IV perfusion, blood sampling) is strictly prohibited. DCath are handled by trained nurses (i.e., bearing sterile gown, mask, hat, gloves) in strictly surgical aseptic conditions (ie, sterile drape protection at time of connecting and disconnecting extracorporeal blood circuit). At the time of connection, remaining blood material and antithrombotic solution within each line of DCath is withdrawn with a 10-ml syringe and discarded. Isotonic saline (5 to 10 ml) is then flushed vigorously in each line of DCath to clean and probe resistance of DCath. Extracorporeal blood circuit is then initiated by connecting each DCath line to the corresponding blood line and blood pump is launched and brought progressively to its prescribed speed. At the time of disconnection, blood pump is stopped, and blood is flushed back and returns to patient (about 200-300 ml of saline) by means of online rinsing option alternatively on the arterial and venous side. Blood lines are disconnected, and each line of DCath is filled and locked with a mixture of saline and 0.3% citric acid solution (2.5 to 2.8 ml per catheter line).
Luer-lock cap is then screwed. DCath are wrapped in a split sterile gauze and a transparent sterile adhesive waterproof air-permeable dressing is applied and kept until next dialysis session.
- 4.4.
Arteriovenous access management
Arteriovenous fistula or grafts are handled with particular care and strictly hygienic conditions relying on betadine as skin disinfectant, using sterile material, drape and gloves as well as mask, gown and cap for the operator at the time of access handling. Needling is performed by trained nurse with fistula needle of 15 gauges in majority of patients using laden rope method.
- 5.
Clinical performances assessed
Baseline clinical performances consisted in six key performance indicators that included the effective blood flow (ml/min), venous pressure (mmHg), vascular access recirculation (VA.REC) (%), single pool Kt/V, double pool Kt/V and convection volume (l/session).
These indicators were measured in the six following vascular accesses: native arteriovenous fistula (AVF), arteriovenous graft (PTFE)(AVG), right femoral DCath (RFDC), right internal jugular DCath (RIJDC), left internal jugular DCath (LIJDC) and Thomas Shunt.
In addition, cumulative clinical performances comparing DCath and grouped AVA over a 30-month follow-up period were performed.
- 5.1.
Blood flow (QB, ml/min)
Blood flow measurement was performed by means of bubble transit time on 1 meter of a calibrated segment of the arterial line27. This method is currently used in our unit and fits perfectly with Transonic data. Calculation of effective blood flow relies on the following formula:
- 5.2.
Total blood volume processed (TBVP, L/session)
Total blood volume processed was calculated from dialysis machine as the product of the effective blood flow (QB) times treatment time (tHD) as TBVP = QB x tHD
- 5.3.
Vascular access recirculation (VA.REC, %)
Total recirculation (T.REC) was calculated by using urea dosing issued from three blood samplings (artery (ART) and venous (VEN) sampling, then followed by a second artery sampling after 2 minutes stop of blood pump (ART
+2)) as follows
27,28:
This method has been validated in our unit and used as standard of care for years. Results fit perfectly with recirculation obtained with Blood Thermal Monitoring device which also assesses total recirculation. When compared to Transonic data, it has been shown that 10% was coming from the cardiopulmonary bypass created by the arteriovenous bypass
16,29. A 10% value of cardiopulmonary bypass was then subtracted from arteriovenous access measurements but not from tunneled central venous accesses as follows:
Dialysis dose delivery was assessed with three key indicators: firstly, the urea clearance expressed as fractional urea clearance (i.e., ureaKt/V), or its surrogate using ionic clearance (online clearance measurement, OCMKt/V)30,31 and as total urea clearance (Kt) delivered per session (i.e., liters per session) to quantify small molecules clearances30,32,33; secondly, the total ultrafiltration volume (liter per session) or convective dialytic dose used as surrogate marker of middle and large molecule clearances34; thirdly, percent reduction of ß2M (%) per session.
- 5.4
Urea Kt/V
Urea Kt/V was calculated from pre and postdialysis blood sampling using the single-pool
35 (sp) and equilibrated (e) double-pool Kt/V formula from Daugirdas
36 as follows. Of note, postdialysis blood sampling was performed after reducing blood pump down to 50 ml/min for two minutes.
where WL is the weight loss during the session, BW the body weight and t
HD the effective treatment time
- 5.5.
Ionic dialysance and ocm Kt/V
Ionic dialysance Kt/V and ocmKt/V was measured and calculated from dialysis monitor using integrated ionic dialysance (Kocm) performed across dialysis session, effective HD machine treatment time (tHD) and total body water (V) derived from Watson formula by default.
- 5.6
Total Kt (TKt, L/session)
Total Kt was calculated as the product of ionic clearance (Kocm) and effective treatment time (tHD) of dialysis session as TKt = Kocm x tHD
- 5.7.
Total ultrafiltration volume (VUF, L/session)
The total ultrafiltration volume (VUF) is the sum of online substitution volume infused during the HDF session (VSUB) plus intradialytic weight loss (WL) to correct fluid overload. This indicator is used as surrogate of convective dialytic dose delivered per session34.
- 5.8.
Percent reduction of β2-Microglobulin (PRβ2M)
Percent reduction of β2M was used as a marker of HDF efficiency as patients were receiving HDF treatment
34. Postdialysis β2M was corrected for hemoconcentration using Bergstrom formula
37
- 5.9.
Normalized protein catabolic rate (nPCR)
nPCR (g/kg/24h) was calculated from urea kinetic modeling using the three points method38 (pre/post and pre next dialysis session)
Blood samples were analyzed on the same day in the central laboratory of our hospital using validated autoanalyzer methods.
- 6.
Statistics
Statistical analyses were performed using JASP Software 0.17.1 (University of AMSTERDAM). Normality and variance equality tests were made for all data, and statistical significance level was set to p <0.05 for all analyses. Continuous variables were reported as means (SD) or as medians [25-75%] depending on whether the data were normally distributed or not. Categorical variables were reported as percentages with number in parentheses. Unpaired normally distributed continuous variables were tested for difference using unpaired t-test. Unpaired non-normally distributed continuous data were analyzed using Mann-Whitney test. Pearson’s or Spearman’s test were used for correlation analyses depending on whether data were normally distributed or not, respectively.
4. Discussion
In this retrospective study consisting of 68 maintenance dialysis patients, we assessed precisely clinical performances delivered throughout tunneled central venous catheters (DCath) and compared them to various arteriovenous accesses (AVA) used routinely in our dialysis facility. For this purpose, we used monthly quality control measures with 30 months followed-up. As most original finding of our study is the fact that DCath were shown to deliver high blood flow (400 ml/min) and achieved high volume hemodiafiltration on a regular basis with comparable results to AVA. As second finding, the study highlighted the fact that dialysis dose delivered, either for small sized molecules (total urea clearance) or middle-sized molecules (total ultrafiltration volume and β2M reduction rate) was almost similar with DCath and AVA, was higher than the targets recommended by clinical best practice guidelines and remained stable over time up to 30 months. The main difference relies on the fact that recirculation with DCath was significantly higher (≈7%) than AVA resulting in a total urea clearance with DCath slightly lower than AVA. Interestingly, this recirculation didn’t impact the total ultrafiltration volume which remained almost similar with DCath and AVA. In all cases, dialysis performances and key performance indicators were not affected while DCath were used as mainstream vascular access.
This finding is in quite contrast with previous studies reporting that tunneled CVC tends to be associated with a reduction of dialysis dose delivered due to the limited blood flow and increase in vascular access recirculation, but also precluding use of high volume hemodiafiltration21,39,40. In fact, the apparent superiority of DCath compared to other tunneled central venous catheters relies on three main components: firstly, to the geometry and the design of cannulas that are specifically engineered (two independent cannulas, adjustable to patient anthropometry, with side holes at the tips) to provide high blood flow with relatively low blood flow resistance; secondly, to the careful way of inserting and positioning tips in central venous system at time of implantation, mainly at junction of superior vena cava and right atrium for internal jugular vein site, but alternatively in inferior vena cava for femoral site; thirdly, to the strict and careful catheter handling protocol consisting in using locking solutions (antithrombotic, fibrinolytic) to maintain or restore catheter flow permeability41.
Each of these components has been clearly documented in the scientific literature13. Two single cannulas made of soft silastic with adequate inner lumen (≥ 2 mm) and distal side holes tend to provide higher and more sustainable blood flow during dialysis session than double lumen semi-rigid polyurethane conventional catheters12,13,21,42. Tips positioning at the junction of superior vena cava and right atrium also tend to reduce risk of poor blood flow occurring during dialysis session due to the hypovolemia associated with the ultrafiltration43. In addition, side holes present at the tips of catheters keep lines in the core flow of the vein and prevent sucking vein walls. Higher flow achieved with side holes catheters has been challenged in some studies by thrombosis and infectious risk14,15.
Silastic cannulas made of soft rubber tend to be the most hemocompatible material reducing platelet adhesion, catheter thrombosis risk and bacterial adhesion44. This mechanistic interpretation of phenomenon has been illustrated in some catheter flow modeling studies from simulation in silico experiment45. Another important factor relies on the strict implementation of best practices catheter handling developed by nursing team46. Aside strict aseptic conditions applied to catheter handling, a new science of catheter locking solution has been developed and has been shown to be very efficient in maintaining catheter lumen patency47-50. It is not our intent to review catheter locking practices, but we refer readers interested to recent comprehensive reviews on this topic. In our unit, locking solutions have been always at the heart of catheter care practices. We moved from conventional heparin locking solution to more personalized and adaptative locking solutions involving more citrate-based solutions and/or fibrinolytic solutions guided by blood flow and/or pressure regime changes in the recent time.
Strength of our study relies on the precise quantification and comparison of dialysis performances achieved with DCath compared to conventional arteriovenous accesses (AVF, AVG) used to deliver high volume hemodiafiltration in a relatively large number of dialysis patients followed up for 30 months. This is in clear contrast with a previous large cohort study showing that high volume HDF (>21 l) was achieved in 33% of prevalent patients51. Safety and risk assessment associated with DCath use is currently assessed in another multicenter study.
Our study has weaknesses that we want to highlight. Firstly, this is a single center study performed by well-trained physicians and nursing team dedicated to vascular access management and therefore transferability to larger centers may be questionable. Secondly, the number of patients may appear limited, but this is due to the academic hospital-based dialysis facility with large turnover of patients. Thirdly, a comparative economic evaluation between DCath and AVA was not done in this study.
As our study indicates, the use of tunneled CVC is not associated with worst vascular access scenario in dialysis patients. As such, by means of DCath, we were able to perform high volume hemodiafiltration with high blood flow in all patients for sustained period up to 30 months. This is a quite reassuring finding, since it makes possible to consider treating fragile patients (i.e., elderly, diabetic, cardiac) or patients without AVF or AVG by most efficient convective-based treatment modalities, currently high volume hemodiafiltration. In other words, tunneled central venous catheter should not be considered as a limiting factor in providing most efficient treatment modality provided the right tunneled CVC is used.