**4. Types of vascular access**

Vascular access involves the insertion of a catheter into a large vein to provide access for the CRRT machine. There are several types of vascular access options available for CRRT for placement of central venous catheters (CVCs). Either subclavian vein, internal jugular vein or femoral vein can be used for CVC placement. CRRT capable catheters need to be able to handle blood flow of 200–250 ml/min. Internal jugular vein is the preferred site.

Given that vascular access is required for CRRT, the introduction of a vascular catheter into a vein always poses a risk of infection. The femoral site has been commonly known to carry a higher risk of infection as compared to other potential sites of vascular access such as jugular or subclavian veins. Typical risk factors for infection include improper catheter care, prolonged catheterization, immunocompromised status, and underlying comorbidities.

Interestingly, a large trial in JAMA in 2008 (by Parienti et al.) [5] found that, in terms of infections and its complications, jugular and femoral sites were equivalent. However, internal jugular vein insertion may be preferable in obese patients.

According to a systematic review and meta-analysis published in the Journal of Critical Care in 2019 (by Clark et al.) [6], the overall rate of catheter-related bloodstream infection (CRBSI) in CRRT was approximately 7.4 per 1000 catheter-days. However, the specific infection rates associated with femoral vascular access were not explicitly mentioned in the study.

The right internal jugular vein is the preferred site for a temporary catheter in CRRT due to its direct route to the superior vena cava. The catheter tip should be positioned at the junction of the SVC and the right atrium. The left jugular vein has a more indirect path to the right atrium, potentially causing inadequate blood flows and filter issues. The femoral veins are a secondary option due to their accessibility. Subclavian veins are used as a last resort due to concerns about stenosis, especially if the patient may require an AVF or AVG in the same arm in the future.

Subclavian vein stenosis in CRRT is a potential complication, though its exact incidence varies. Prolonged catheter use, catheter-related factors, and individual patient characteristics contribute to its development. Rates range from 1% to 10%. Careful catheter insertion techniques, appropriate catheter size selection, and regular monitoring are important for mitigating the risk. Prompt evaluation and intervention, such as percutaneous transluminal angioplasty (PTA), may be necessary if subclavian vein stenosis occurs to maintain effective CRRT.

A recent study by Xu et al. [7] evaluated the safety and efficacy of a newly developed PTA technique for maintaining vascular access in patients undergoing CRRT. The study found that the PTA technique was safe and effective in maintaining vascular access in patients with central venous stenosis, and it significantly reduced the incidence of catheter-related infections and thrombosis. The study recommended the use of the PTA technique for the maintenance of vascular access in patients with central venous stenosis undergoing CRRT.

Transhepatic and trans lumbar approaches are alternative methods for dialysis access when traditional options are not possible. The transhepatic approach involves inserting a catheter through the liver, while the trans lumbar approach involves accessing the lumbar vein through the lower back. These methods require expertise in interventional radiology and carry risks such as infection and catheter dysfunction. They are temporary solutions until more permanent access can be established.

In summary, vascular access is a critical aspect of CRRT, and the choice of access site should be individualized to each patient's clinical condition.

## **5. Dialyzer membrane**

In both IHD and CRRT, standard dialyzers are used. Semipermeable hollow fiber dialyzers are the current standard of care. KDIGO suggests using a biocompatible membrane for both IHD and CRRT (2C) [1].

There are many distinct types of membranes available. Modified cellulose and synthetic membranes such as ones made from Poly sulfone are thought to be compatible membranes. All dialyzers activate the complement system. The dialyzer membrane that activates the complement system such that it leads to fever, hypotension, vasodilation, leucopenia, and hypoxia are "bioincompatible". It should be noted that a Cochrane meta-analysis in 2008 [8] did not show any difference between bioincompatible and biocompatible membranes.

The other property to be considered is flux. Flux is the permeability of dialyzer membrane. Clearance of beta-2 microglobulin defines low (<10 cc/min), medium (10–20 cc/min) and high (>20 cc/min) flux, respectively. It has been a matter of debate whether high flux membranes would be more beneficial as it can clear larger solutes. To this point, there is some evidence from a couple meta-analyses that showed potential benefit for high flux dialyzer membrane in hemodialysis patients [9]. A well-designed RCT is needed to further study this.
