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37 Vascular Access for Renal Replacement Therapy 433
Catheter Insertion Technique
Although KDIGO guidelines recommend non-tunneled dialysis catheters (NTDCs)
to initiate renal replacement therapy (RRT) in the ICU, long-term tunneled dialysis
catheters (TDCs) are a valid option when the recovery of kidney injury is unlikely
and prolongation of RRT is required [3]. To reduce the rate of infectious complications, TDCs have a subcutaneous course and are equipped with a polyester cuff that
acts as a barrier to microorganism migration through the skin, promoting local
fibrous tissue to prevent TDC displacement.
Moreover, with their larger diameter, TDCs allow for a higher extracorporeal
blood flow compared to NTDCs. The external diameter size of NTDCs varies
between 11.5 and 13.5 French (Fr), while TDC diameter size is between 14.5 and
16 Fr [17, 18]. Drawbacks related to TDCs are mainly due to the fact that insertion is
a cumbersome procedure, often requiring a surgical or radiological room and
fluoroscopic guidance to ensure that the tip is placed in the upper to mid-right
atrium. Patient conditions such as uncorrectable coagulopathies, uncontrolled sepsis,
and chronic infections are contraindications to TDC insertion [18].
Accurate selection of the appropriate site, the patient’s body habitus, clinical
conditions, and adequate catheter length should be addressed before starting the
procedure. Adequate skin preparation and aseptic procedures must be used during
catheter insertion.
Although the blind landmark technique for dialysis catheter insertion has been
used for several decades, ultrasound (US) guidance for catheter placement is now
recommended by international guidelines, as it has been proven to increase the rate
of successful catheter placement and reduce the rate of complications [3, 10]. US
guidance allows operators to assess vein size, patency, and anatomical abnormalities. With the utilization of real-time US guidance, the operator can visualize the
needle advancement and vein puncture under constant US control [19]. A 2011
meta-analysis evaluated data from seven randomized controlled trials (RCTs) comparing the use of real-time US guidance with the anatomic landmark technique in the
insertion of NTDCs and TDCs. Most of the catheters were placed in the right jugular
vein. Results of the meta-analysis showed that real-time US guidance, compared to
the landmark technique, decreased the risk of catheter placement failure, the risk of
carotid artery puncture, and the risk of hematoma [20].
In a 2010 study conducted in a single ICU, 110 patients underwent femoral vein
catheterization to initiate RRT. The patients were divided into two groups to
compare the anatomical landmark technique for femoral vein catheter insertion
with real-time US guidance. The successful insertion rate was 80% using the
anatomical landmark technique, whereas with real-time US guidance, the rate was
98% (P = 0.002) [21].
Current eviden
dialysis catheter (DC) placement [3, 10, 16]. Following DC placement using the
Seldinger technique, it is crucial to confirm the correct position of the catheter and
the tip before initiating RRT, either through chest radiography or fluoroscopy.
ce strongly advocates for the use of real-time US guidance for
434 F. Valente et al.
a
Fig. 37.2 In panel A, the correct position of an NTDC in the jugular vein; panel B shows the tip
malposition of an NTDC
b
For non-tunneled dialysis catheters (NTDCs), the tip should be positioned at the
junction of the superior vena cava and right atrium. Conversely, for tunneled dialysis
catheters (TDCs), the tip should be in the upper right atrium (Fig. 37.2).
The precise positioning of the tip in a large vein is crucial, as dialysis efficiency
depends on
adequate blood flow. Therefore, the length of a femoral catheter should
be at least 24 cm or longer, allowing the tip to be placed in the inferior vena cava
[3, 16].
Dialysis Catheter Complications
The skill of the operator, the site of insertion, the severity of the patient’ s illness, and
the use of imaging may influence outcomes and complications in dialysis catheter
(DC) insertion. DC-related complications can be classified into two groups: early
and delayed (see Table 37.1).
• Early complications
– Vascular injury
– Pleural injury
– Cardiac arrhythmias
– Air embolism
– Early dysfunction
Early
complications
tion procedure may cause arterial and/or venous vascular injuries. Low-severity
vascular injuries include arterial puncture and hematoma. Severe-degree injuries,
are mainly related to procedural events. The catheter inser-
37 Vascular Access for Renal Replacement Therapy 435
Table 37.1 Early and
delayed complications associated with dialysis catheter
(DC) placement
Early DC complications Delayed DC complications
Artery puncture Exit site infection
Hematoma CRBSI
Vessel laceration Thrombosis
Hemothorax Fibrin sheath
Pneumothorax Central venous stenosis
Air embolism Inadequate blood flow
Brachial plexus injury
Cardiac arrhythmia
Cardiac tamponade
Retroperitoneal bleeding
Note: DC dialysis catheters
a
femoral site
a
sometimes requiring emergent surgery, encompass vessel laceration/perforation,
hemothorax, hemopericardium, and hemomediastinum. Con cerning femoral vascular injury, albeit rare, retroperitoneal bleeding may occur [22].
Among acute complications, pleura injury may occur. Vinson et al. reported,
although with non-dialysis catheters, an incidence of pneumothorax higher during
subclavian vein than internal jugular vein placement (2.3% vs.
P < 0.001) [
23].
0.1%,
Cardiac arrhythmias may complicate the procedure due to an over-insertion of the
guidewire in the right heart with an estimated incidence of 42% [
24]. In most cases,
arrhythmias disappear with the partial retraction of the guidewire. For this reason,
electrocardiographic monitoring should be used for the early detection of arrhythmias during DC insertion in the neck.
Although infrequent, venous air embolism may complicate the DC’s insertion
[22]. Early DC dysfunction may be due to tip malposition or catheter kinking.
• Delayed complications
– DC-related infections
– Late dysfunction
DC-related infections are a major cause of morbidity, mortality, and healthcare
costs. However, the overall incidence of catheter (non-dialysis and dialysis) infections has declined in the ICU due to improvements in infection control measures
[25–27]. Different infection modalities have been identified:
(a) Extraluminal microbial colonization of the insertion site may promote bacterial
migration through the skin breach at the site of catheter placement (extraluminal
pathway).
Contamination
(b)
of catheter hubs during manipulation may spread infection
through the catheter’s inner side (intraluminal pathway).
436 F. Valente et al.
(c) Although less common, DCs may become infected by hematogenous spread
from other sources of infection [13].
The definition of catheter-related bloodstream infection (CRBSI), according to
the 2019 KDOQI guidelines, is based on the presence of clinical manifestations
(fever, chills, and hemodynamic instability) and at least one positive blood culture
from a peripheral source (dialysis circuit or vein) with no other apparent source. This
includes either positive semiquantitative (>15 CFU/catheter segment, hub, or tip) or
quantitative (>10
2
CFU/catheter segment, e.g., hub or tip) cultures, where the same
organism (species and antibiogram) is isolated from the catheter segment (e.g., hub
or tip) and a peripheral source (dialysis circuit or vein) blood sample [
16].
For patients in whom the diagnosis of CRBSI is strongly suspected or confirmed,
given the potential for life-threatening sepsis and metastatic localizations, a broadspectrum antibiotic therapy should be promptly initiated. Consideration should be
given to DC removal, and a new DC should be placed at a different site. Narrowspectrum antibiotic therapy should be initiated once the culture results become
available [16, 28].
Late dysfunction, occurring after successful initial use, is primarily related to
thrombotic complications. Intracatheter and/or pericatheter thrombosis, as well as a
fibrin sheath around the DC, may occur. In the case of catheter dysfunction due to
intraluminal thrombosis, a thrombolytic agent such as urokinase or alteplase can be
left to dwell for 20 – 60 min in each DC port to restore function [16]. If persistent DC
malfunction is encountered despite conservative management, DC removal and
replacement at another site should be performed. An alternative option might be a
DC exchange over a guidewire, especially when other insertion sites are not available. A 2016 study in the ICU showed that NTDC’s guidewire exchange, in case of
dysfunction, did not increase the risk of DC colonization/infection when compared
to de novo percutaneous venipuncture insertion [29].
Finally, as a late complication, stenosis of the host vessel may occur due to
endothelial damage triggered by prolonged contact between the catheter and the vein
wall [30].
Dialysis Catheter Maintenance
DC utilization should be reserved exclusively for RRT. Blood sampling, hemodynamic monitoring, parenteral nutrition, fluids, and drug administration should be
discouraged to minimize complications related to DC [
Universa
l p
recautions, using sterile materials and aseptic procedures, should be
applied whenever a DC is manipulated, connected, and disconnected from the
extracorporeal circuit [31].
Continuous
vigilance and adherence to a DC bundle of infection control and care
procedures are imperative to reduce complication rates.
10].
37 Vascular Access for Renal Replacement Therapy 437
To prevent intracatheter thrombosis and maintain catheter patency during the
interdialytic interval, locking solutions are utilized. Unfractionated heparin (UH) is
the most widely used. Citrate has raised interest as a locking solution due to its
anticoagulant properties, antibacterial activity, and prevention of biofilm formation
in vitro [
no differences were found in terms of reducing catheter thrombos is and catheterrelated bloodstream infections (CRBSI) when comparing a UH locking solution to a
4% citrate locking solution [34].
developed to enhance DC patency rate and prevent infections. Due to the lack of
robust evidence, so far, they are not recommended in critically ill patients in ICU;
moreover, they have higher costs and the potential of promoting antibiotic resistance
[33, 35].
thrombotic complications represent a crucial area for future research. Despite progressive improvements in DC materials, biocompatibility, lumen, and tip designs,
more studies are n eeded to identify an ideal DC that can provide an adequate lifespan
while reducing dysfunction and CRBSI rates.
32, 33].
In a 2019 RCT involving critically ill patients with a non-tunneled DC in the ICU,
DCs with antithrombotic and/or antimicrobial impregnated material have been
Innovations to enhance catheter patency and lifespan and minimize infectious and
Conclusions
In conclusion, successful outcomes in dialysis catheter (DC) insertion are influenced
by various factors, including the operator’ s skill, insertion site, patient’s illness
severity, and the use of imaging. Complications can be broadly categorized into
early and delayed events.
Early complications primarily stem from procedural events, encompassing vascular and pleural injuries, cardiac arrhythmias, air embolism, and early dysfunction.
These events underscore the importance of precision during catheter insertion, with
attention to potential complications such as arterial punctures, hematoma, and, albeit
rarely, retroperitoneal bleeding. Pneumothorax risks, as reported in previous studies,
emphasize the significance of careful site selection.
Cardiac a
and monitoring during the procedure. Early dysfunction, often linked to tip malposition or catheter kinking, necessitates prompt identification and corrective
measures.
On the
dysfunction, and central venous stenosis. Infections pose a significant threat to
patient well-being and incur substantial healthcare costs. The decline in infection
rates, particularly in the ICU, reflects advancements in infection control measures.
Understanding different infection modalities, including extraluminal and
intraluminal pathways, is crucial for effective preventive strategies.
rrhythmia
other hand, delayed complications include DC-related infections, late
s and venous air embolism, highlight the need for vigilance
438 F. Valente et al.
Late dysfunction, often associated with thrombotic complications, may necessitate interventions such as thrombolytic agents or, in persistent cases, DC replacement. The potential development of central venous stenosis underscores the
importance of considering long-term impacts on vessel health.
In summary, ongoing research and improvements in catheter materials, insertion
techniques, and infection control measures remain essential. Identifying ideal DC
characteristics that balance lifespan, functionality, and infection prevention is a key
avenue for future studies. The field’s dedication to addressing complications and
optimizing outcomes contributes to enhancing patient safety and the overall effectiveness of dialysis catheterization.
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Chapter 38
Anticoagulation Strategies in Continuous
Renal Replacement Therapy
Antonio Fioccola and Gianluca Villa
Introduction
Non-pharmacological strategies play a crucial role in mitigating membrane fouling
during continuous renal replacement therapy (CRRT). Membrane fouling, primarily
caused by clogging and clotting phenomena, significantly reduces treatment efficiency and lifespan of CRRT filters. Solutions bag changes and circuit substitutions
due to pore occlusion and clot formation contribute to treatment interruptions,
leading to ineffective treatment delivery. To address these challenges,
non-pharmacological interventions focus on reducing the filtration fraction applied
during CRRT, thereby minimizing hemoconcentration inside the hollow fibers of the
hemodiafilter. This reduction in filtration fraction helps mitigate the accumulation of
plasma proteins, platelets, red blood cells, and coagulation factors near the membrane surface, thus reducing the incidence of clogging and clotting. Pharmacological
strategies, on the other hand, aim to prevent membrane clotting and fouling by
inhibiting coagulation factors and platelets within the hemodiafilter. Systemic
anticoagulation with unfractionated heparin and regional citrate anticoagulation are
among the most commonly employed pharmacological techniques. While
unfractionated heparin inhibits coagulation factors IIa and Xa, regional citrate
anticoagulation chelates ionized calcium, a crucial coagulation cascade cofactor,
thereby preventing clot formation within the circuit. This comprehensive review
explores the efficacy, mechanisms, and considerations associated with both
non-pharmacological and pharmacological strategies in reducing membrane fouling
Supplementary Information The online version contains supplementary material available at
https://doi.org/10.1007/978-3-031-66541-7_38.
A. Fioccola (
Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of
Florence, Florence, Italy
e-mail: antonio.fioccola@unifi.it; gianluca.villa@unifi.it
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
A.
Cotoia et al. (eds.), Nutrition, Metabolism and Kidney Support,
https://doi.org/10.1007/978-3-031-66541-7_38
✉) · G. Villa
441
442 A. Fioccola and G. Villa
during CRRT. By elucidating the underlying principles and practical applications of
these strategies, clinicians can optimize treatment efficacy, prolong filter lifespan,
and improve patient outcomes in critically ill populations undergoing CRRT.
Non-pharmacological Strategies to Reduce Membrane Fouling
Treatment interruptions during continuous renal replacement therapy (CRRT) (i.e.,
treatment downtime) reduce the effective time of treatment and negatively impact
treatment efficiency, enhancing the difference between the prescribed and the
].
effective delivered dose [
undergoing CRRT, solutions bag changes (e.g., dialysate, replacement fluids, and
effluent) and circuit substitution due to pore occlusion and clot formati on throughout
the filter are the most frequent. These two latter phenomena are, respectively, known
as clogging and clotting and globally named membrane fouling. The membrane
fouling decreases filter lifespan and progressively diminishes the surface of the
membrane available for solutes exchange, both in convective and diffusive modalities, further increasing the difference between prescribed and effective delivered
doses. Clogging is the protein and red cell debri s deposition on the inner layer of the
filter membrane and leads to membrane pore occlusion [
describes this event as “protein cakes” formation [3, 4
increase in transmembrane pressure (TMP), i.e., the press ure difference measured at
the blood versus the effluent compartments of the hemodiafilter. The development of
clots throughout the hollow fibers (on the filter’s longitudinal axis) is also known as
membrane clotting. The clots in the hollow fibers increase the filter pressure drop,
i.e., the difference between the prefilter and the post-filter pressure. Once the
transmembrane pressure or the filter pressure drop has increased rapidly or has
reached a threshold of high values, the CRRT machine identifies conditions where
exchanges throughout the membrane may be inefficient due to clotting or clogging,
and it stops the treatment to allow the practitioner to substitute the extracorporeal
circuit. This event is an important cause of downtime, effective delivered dose
reduction, blood loss and wastefulness of healthcare resource
5, 6].
[
Non-pharmacological strategies are proposed in clinical practice to reduce
clogging and clotting phenomena, mainly through the reduction of filtration fraction
applied during the treatment. Filtration fraction (FF) is the ratio between plasma
water removed by ultrafiltr ation on the total amount of plasma water entering into the
hemodiafilter. The higher the FF, the more significant the hemoconcentration inside
the hollow fibers
and coagulation factor concentration increases nearby the inlet layer of the membrane surface, clogging and clotting frequently develop. The FF during continuous
veno-venous hemofiltration (CVVH) and continuous veno-venous hemodiafiltration
of the hemodiafilter.
1
Among causes of treatment interruptions in patients
2].
The literature also
].
Pore occlusion causes an
When plasma protein, platelet , red blood cell,
38 Anticoagulation Strategies in Continuous Renal Replacement Therapy 443
(CVVHDF) depends on several treatment settings and is calculated as follows
(Eq. 38.1):
Filtration fraction FFðÞ=
Filtration fraction determinants. Q
= plasma flow. Hct = hematocrit. Q
Q
p
Q
uf
=
Q
Qb 1 - HctðÞþ Q
p
= total ultrafiltration rate. Qb = blood flow.
uf
= prefilter replacement fluids
r(pre)
Q
uf
r preðÞ
ð38:1Þ
In order to reduce the FF, the prescriptioner can adopt three main strategies
[7]. The first is to choose diffusive (continuous veno-venous hemodialysis,
CVVHD) instead of convective (CVVH, CVVHDF) techniques. In pure diffusive
modalities (CVVHD) and in the absence of net ultrafiltration, the total ultrafiltration
rate, and thus the FF, is equal to 0. The increase in pre filter replacement (Q
r(pre)
instead of post-filter replacement fluids, is the second alternative to dilute the plasma
water and reduce hematocrit before the filter inlet during CVVH or CVVHDF
(Eq.
38.1). The increase in blood flow rate is another way to reduce FF, particularly
in those treatment performed without RCA. Several studies have shown a decreased
average filter lifespan when performing an EBP without anticoagulant drugs [7–
10]. Nevertheless, in some cases, there is still indication for a no-anticoagulation
treatment. Two possible examples in which this strategy can be used are patients
with absolute contraindications to anticoagulation techniques (see following paragraphs) and patients that need short cycles of extracorporeal blood purification
(EBP), as in the intermittent hemodialysis (IHDs) or in the prolonged intermittent
renal replacement therapies (PIRRTs).
In these circumstances, the non-pharmacological strategies to increase circuit
patency are essential, and the clinician must be extremely careful to enhance them
in phase of treatment prescription, trying to decrease the FF. The best approach to
increase filter patency would be to employ, whenever possible, both
non-pharmacological and pharmacological strategies, in order to prevent clogging
and clotting. Therefore, with an increase of available membrane pores (higher
treatment efficacy) and a longer filter duration, the clinician can achieve a more
efficient treatment, with positive outcomes for the patients and lower costs for the
health systems (Fig. 38.1).
),
Pharmacological Strategies to Reduce Membrane Clotting
Systemic anticoagulation with unfractionated heparin (UFH) and RCA are the two
most employed pharmacological strategies to reduce membrane fouling [11]. Other
less common methods for CRRT anticoagulation are systemic low molecular weight
heparin (LMWH), direct thrombin antagonists (e.g., argatroban) [12] or platelet
inhibitors, and regional anticoagulation with prefilter heparin and post-filter