Renal Replacement Therapy in Intensive Care Unit

Abstract

This chapter presents a comprehensive overview of the latest advancements in renal replacement therapy (RRT) including Continuous Renal Replacement Therapy (CRRT), focusing on key topics such as acute kidney injury (AKI), renal replacement techniques, patient selection, vascular access, dialyzer membranes, anticoagulation strategies, optimal RRT prescription, drug dosing, laboratory monitoring, and complications of RRT. The incidence of AKI in intensive care unit (ICU) is estimated to be from 5% to 50%. It carries substantial morbidity and mortality. In this chapter, we aim to emphasize the significance of AKI in ICU and indications that necessitate effective RRT. The chapter explores various renal replacement techniques with emphasis on CRRT, including continuous venovenous hemodialysis, hemodiafiltration, and hemofiltration. The clinical indications and contraindications for CRRT are discussed. Vascular access options, dialyzer membrane characteristics, and anticoagulation strategies are examined, providing insights into their impact on treatment outcomes and patient safety. Additionally, highlighted points include the importance of optimal RRT prescription, drug dosing adjustments, and laboratory monitoring in CRRT. It addresses potential complications associated with CRRT and offers strategies for their prevention and management. Overall, this book chapter aims to serve as a valuable guide for healthcare professionals, providing them with updated information to optimize patient care and improve outcomes in individuals with AKI undergoing RRT in ICU.

1. Introduction

1.1 Acute kidney injury

Acute kidney injury (AKI) is a widespread problem. It is often used interchangeably with acute renal failure. The incidence of AKI in intensive care unit (ICU) is wide ranging from 5% to 50% and specific to the type of ICU. AKI can have quite a profound impact on the patient and is associated with severe morbidity and mortality. Mortality can range from 40% to >60%. There are consensus definitions of AKI, and they are broken down into three types.

1.2 KDIGO criteria

An AKI can be defined or diagnosed by various criteria. The most used criteria are the KDIGO (Kidney Disease Improving Global Outcomes) criteria. Others include RIFLE (Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease) and AKIN (Acute Kidney Injury Network) criteria. KDIGO defines AKI as:

• Increase in serum creatinine by greater than or equal to 0.3 mg/dl within 48 hours

• Increase in serum creatinine greater than equal to 1.5 times baseline which is known or presumed to have occurred within the past 7 days or

• Urine volume less than 0.5 ml/kg/h for 6 hours.

1.3 Types of AKI: pre-renal vs. intrinsic vs. post-renal

AKI can be broken up into pre-renal, intrinsic, post-renal causes. Pre-renal is caused when the kidney has ischemia due to decreased generalized perfusion or specifically to the kidney. This can occur through many processes such as hypovolemia, hypotension, hemorrhage, acute heart failure exacerbation, ACE inhibitor use etc.

Intrinsic renal disease can be caused by many varied factors. Renal vascular disease can affect small and large vessels within the kidney. These can be caused by vasculitis, microangiopathic and hemolytic anemias, malignant hypertension, etc. Intrinsic disease can also be glomerular disease that can be primary or secondary to systemic disease. This can cause nephritic or nephrotic pattern of disease. Tubular or interstitial can cause intrinsic disease that causes AKI, also known as ATN, these are caused by ischemic or nephrotoxic exposure, such as medications or contrast dye.

Lastly, post-renal disease is obstructive and can be anywhere in the urinary tract. This can be due to prostatic disease, nephrolithiasis, cancer, etc.

1.4 KDIGO criteria - AKI severity staging

KDIGO guidelines [1] split severity into three groups based on specific creatinine levels and urine output (Table 1).

Stage	Serum creatinine	Urine output
Stage 1	Increase in sCr to 1.5–1.9 times baseline Increase sCr by ≥0.3 mg/dl	UOP <0.5 ml/kg/h for 6–12 hours
Stage 2	Increase in sCr to 2.0–2.9 times baseline	UOP < 0.5 ml/kg/h for ≥12 hours
Stage 3	Increase in sCr to 3 times baseline Increase in sCr to ≥4.0 mg/dl	Improved hemodynamic stability compared to standard IHD Anuria for ≥12 hours

Table 1.

KDIGO AKI stages [1].

Other guidelines such as RIFLE use reduction in GFR as well. Though both serum creatinine and urine output can be used to diagnose, serum creatinine tends to be a stronger predictor of ICU mortality whereas urine output does not independently predict mortality. Some studies suggest that when both criteria were met, elevated serum creatinine and reduced urine output, the risk of death or use of RRT was more strongly correlated. Urine output is also dependent on fluid intake, if the patient has limited fluid intake even a healthy individual cannot meet this criterion. Because of this many experts do not agree on diagnosing of an AKI based solely on urine output.

2. What are the types of renal replacement techniques?

2.1 What is renal replacement therapy?

Renal replacement therapy (RRT) is for patients with severe kidney injury. Hemodialysis is a method that uses a dialysis machine to filter the patient’s blood and remove waste products and any volume surplus. The machine uses catheters that fit into the venous system, arteriovenous fistula (AVF) or arteriovenous grafts (AVGs) that will drain the blood and replace it after it is cycled through.

Blood flows through the hemofilter and comes to a semipermeable membrane, using the process of diffusion to separate waste and volume from the patient’s blood. The smaller contents such as water and electrolytes can be filtered through and larger molecules such as cells and proteins are maintained in the blood. The semipermeable membrane has different pore sizes that can determine what is able to move through, 10–100 angstroms that will allow smaller molecules <5000 Da.

For diffusion to occur a change in concentration must pull certain toxins and water from the blood out of the circulation. A dialysate fluid is used around the semipermeable membrane to provide the concentration difference. Dialysate fluid usually uses bicarbonate as a buffer such that bicarbonate can be added to the blood; it can have low levels of potassium so that potassium from the blood can be pulled out. Dialysate runs countercurrent to the plasma to maximize the solute difference on both sides.

Multiple modalities of RRT are available, categorized as intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT). IHD can be used in patients who are more hemodynamically stable. It can also be used for patients on lower dosing and stable requirement of pressors in ICU at the discretion of nephrologist and critical care physician. They get HD at different intervals depending on need and renal function. CRRT or continuous dialysis is usually 24 hours a day and is used in an ICU setting. There are also hybrid therapies such as sustained low efficiency dialysis (SLED) and extended duration dialysis (EDD). Hybrid therapies are used infrequently, though, this tends to be ICU and institution specific.

CRRT machines can do hemodialysis as described above with diffusive clearance. They can also use hemofiltration which is a convective clearance. The fluids are removed with hydrostatic pressure so that all the toxins and electrolyte abnormalities are removed from the plasma. This can remove small, medium, or large solutes. The greater the fluid movement the more “solute drag” is had, where solutes are moved out of the plasma because of the force of fluid movement. Replacement fluid is then added back to the plasma. The fluid is physiological and contains electrolytes and proteins that are closer to what the body needs or should have. The replacement fluid will have normal concentrations of potassium, bicarbonate, etc. The replacement fluid can be added before the filtration which would dilute the plasma and cause less solute clearance. However, it can prevent clotting and preserve the filter. When added after filtration it is called post-dilution. This can allow for more solute clearance but a higher chance of clotting. A mix of both will allow for balancing the negative consequences. This added fluid will be pulled out through ultrafiltration.

Ultrafiltration works by having fluid cross a semi-permeable membrane. This is done in response to a pressure gradient that can be osmotic, oncotic, or hydrostatic. There can be positive pressure in the plasma pushing fluid out or negative pressure in the dialysate drawing fluid from the plasma. This creates a transmembrane pressure that can control how much fluid is being drawn from the blood.

There are multiple types of CRRT modalities depending on the needs of the patient. These include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF).

CVVH uses hydrostatic pressure with the concept of convection that removes solutes and dialysate fluid is not used. The fluid pulled from the plasma is high, about 20–25 ml/kg/h so there is significant volume depletion. This must be replaced according to the goal that is desired for maintaining even fluid balance or a net negative balance. The addition of fluid dilutes the elevated concentrations of solutes such as urea or creatinine. Predilution also allows urea to be moved out of RBCs into the plasma so once it goes through the filter it can be removed easier.

CVVHD removes solute by diffusion, in which dialysate is used. This is how hemodialysis is done generally and the dialysate fluid runs countercurrent at a rate of 1–2 l/h. The ultrafiltration in this setting is based on desired fluid removal that is desired; no IV fluid replacement is needed.

CVVHDF combines these two modalities. It uses replacement of fluid and dialysate to pull solutes as well as dilute the plasma. The ultrafiltration volume is variable and replacement fluid is used to maintain volume status.

SLED, or sustained low-efficiency daily dialysis, is a term to describe prolonged intermittent kidney replacement therapy (PIRKT). The indication is AKI requiring dialysis and they are patients who are too hemodynamically unstable to tolerate standard IHD. SLED is an alternative to CRRT. CRRT, blood pressures are more stable compared to standard intermittent RRT, because the rate of solute and fluid is slower. Mortality rates are comparable with other forms of RRT, including CRRT. PIKRT should be performed at least three times per week to provide adequate dialysis dose. The time per session ranges from 6 to 18 hours. But typically, is about 8 hours per session. Truly, the length of the session depends on the need of the patient and the hemodynamic stability. A systemic review by Aldahbi et al. published in 2021 [2] found no advantage of using CRRT over SLED in hemodynamically unstable AKI patients.

SCUF (slow continuous ultrafiltration) is a RRT technique that removes excess fluid and solutes from the blood in a gradual and continuous manner. This method operates at a slower rate, minimizing abrupt shifts in fluid and electrolyte balance and reducing the risk of hemodynamic instability in critically ill patients. Unlike CRRT, SCUF primarily focuses on fluid removal rather than solute clearance, making it a suitable choice for patients with fluid overload but stable solute levels. However, it may not be as effective in managing severe electrolyte imbalances or uremic toxins as other dialysis modalities.

Peritoneal dialysis (PD) is another modality that can be used. This involves using the patient’s peritoneal membrane, the thin membrane that lines the abdominal cavity, as a filter to remove waste products and excess fluid from the body. A catheter with two tubes is placed surgically into the patient’s abdomen; one tube is used for inserting the fluid and the other is used for draining the used solution. The solution contains a specific concentration of electrolytes and dextrose that pulls waste products and excess fluids. It remains in the cavity for a certain amount of time, known as the dwell time. This allows the peritoneal membrane to act as a semi-permeable membrane. After the dwell time, the dialysis solution that now has waste products and excess fluid is drained out by gravity using the cycler machine. This process of fluid going in, dwelling, and draining is repeated multiple times during the day or overnight depending on the patient’s requirements. PD has certain advantages, namely: it does not require anticoagulation, it is better tolerated and is cheaper than using an expensive dialysis machine and dialysis nurse or tech. However, it’s not always feasible to emergently place a PD catheter when emergency dialysis is required. It’s preferred that at least 2 weeks be allowed before using the PD catheter after it is inserted. Because the solute and volume clearance are slow, it is not a desirable choice for life-threatening hyperkalemia or pulmonary edema. Patients who have had abdominal surgery or peritoneal scarring cannot use the peritoneum as a dialytic membrane (Table 2).

RRT type	Description	Advantages	Disadvantages
Continuous venovenous hemofiltration	Uses hydrostatic pressure and convection to remove solutes through a filter. Dialysate fluid is not used. High fluid removal rate of 20–25 ml/kg/h, requiring replacement fluids to maintain fluid balance. Predilution dilutes elevated concentrations of solutes and aids in their removal.	Effective removal of solutes and fluid through convection	Requires significant volume replacement
Continuous venovenous hemodialysis	Removes solutes by diffusion using dialysate fluid. Dialysate runs by counter-current at a rate of 1 to 2 l/h. No IV fluid replacement is needed, and ultrafiltration is based on desired fluid removal.	Well-established technique similar to standard hemodialysis	Limited solute clearance compared to other modalities
Continuous venovenous hemodiafiltration	Combines hemofiltration and hemodialysis. Uses both replacement fluid and dialysate to remove solutes and dilute plasma. Variable ultrafiltration volume and replacement fluid are used to maintain volume status.	Enhanced solute clearance compared to CVVH and CVVHD	Increased complexity and requirement for replacement fluid
Sustained low-efficiency daily dialysis	PIRKT for hemodynamically unstable patients. An alternative to CRRT. Solute and fluid removal rate is slower, providing more stable blood pressures compared to standard IHD. Typically performed at least three times per week with session durations ranging from 6 to 18 hours, often around 8 hours.	Improved hemodynamic stability compared to standard IHD	Longer session durations may limit patient mobility and comfort
Slow continuous ultrafiltration	Gradual and continuous removal of excess fluid and solutes. Focuses on fluid removal rather than solute clearance. Slower rate minimizes abrupt shifts in fluid and electrolyte balance, reducing the risk of hemodynamic instability. Suitable for patients with fluid overload but relatively stable solute levels.	Minimizes hemodynamic instability and electrolyte shifts	Limited solute clearance compared to other modalities
Peritoneal dialysis	Uses the peritoneal membrane in the abdomen as a filter. Dialysis solution is introduced into the peritoneal cavity, allowing waste products and excess fluid to diffuse across the peritoneum. Multiple exchanges are performed throughout the day or overnight. No anticoagulation required. Not suitable for emergencies or patients with abdominal scarring. Requires time for catheter insertion and is not ideal for life-threatening hyperkalemia or pulmonary edema.	Convenient and can be performed at home	Limited solute clearance compared to other modalities May not be suitable for patients with high solute loads

Table 2.

RRT types along with their respective advantages and disadvantages [2, 3].

3. Clinical indications and contraindications

CRRT is indicated in severe AKI in hemodynamically unstable patients. Many patients in the hospital have a mild AKI in the setting of acute tubular necrosis, drug induced nephropathy, or pre-renal hypoperfusion, these will require IV fluids and time and, the kidneys will recover. ICU patients tend to have more severe cases of AKI with significant tubular necrosis where fluid resuscitation may not improve the kidney function.

Indications for CRRT [4]:

1. Fluid overload: CRRT can help to remove excess fluid from the body in patients with fluid overload, which can occur because of heart failure, liver failure, or other medical conditions.

2. Electrolyte imbalances: CRRT can be used to correct electrolyte imbalances in the blood, such as hyperkalemia, hypernatremia, and metabolic acidosis.

3. Toxin removal: CRRT can be used to remove toxins from the blood, such as those that result from drug overdoses, poisonings, or metabolic disorders as well as in uremia.

Relative contraindications for CRRT:

1. Bleeding disorders: Patients with bleeding disorders or who are at elevated risk of bleeding may not be good candidates for CRRT, since the anticoagulants used in CRRT can increase the risk of bleeding.

2. Hemodynamic instability: Patients with severe hemodynamic instability, such as those with severe hypotension, may not be able to tolerate the fluid and electrolyte shifts that can occur during CRRT.

3. Active infection: Patients with active infections or who are at elevated risk of infection may not be good candidates for CRRT, since the use of a catheter to connect the patient to the CRRT machine can increase the risk of infection.

4. Coagulopathy: Patients with coagulopathy, or who are at elevated risk of developing blood clots, may not be good candidates for CRRT, since the hemofilter used in CRRT can promote clot formation.

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.

6. Anticoagulation

CRRT requires anticoagulation to prevent clotting of the extracorporeal circuit, which can lead to circuit failure, decreased filter life, and an increased bleeding risk. There are several different methods of anticoagulation for CRRT [10], including:

• Unfractionated heparin (UFH)

• Low molecular weight heparin (LMWH)

• Regional citrate anticoagulation (RCA)

• Prostacyclin

The choice of anticoagulant is based on a variety of factors, including the patient’s underlying medical conditions, bleeding risk, and the preference and experience of the treating physician.

6.1 Unfractionated heparin

UFH is a commonly used anticoagulant for CRRT. It works by binding to antithrombin III, which subsequently inhibits thrombin and other coagulation factors. Dosing is typically titrated to achieve a target activated partial thromboplastin time (aPTT) or activated clotting time (ACT). Typical ranges for aPTT are between 45–60 seconds and 180–220 seconds for ACT. UFH carries the often-cumbersome need for careful monitoring of the patient’s clotting function and frequent dosing adjustments to maintain the target aPTT or ACT.

6.2 Low molecular weight heparin

LMWH is another type of heparin occasionally used for CRRT. It has a similar mechanism of action to UFH, but comparatively holds a lower affinity to antithrombin III. As a result, they have a more predictable anticoagulant effect. As such, LMWH does not require monitoring of clotting function, and dosing is usually based on the patient’s weight.

6.3 Regional citrate anticoagulation

RCA is a method of anticoagulation involving the infusion of citrate into the extracorporeal circuit. Citrate’s mechanism of action is binding to ionized calcium, which is necessary for the activation of coagulation factors. By chelating ionized calcium, citrate inhibits coagulation within the circuit. RCA also requires careful monitoring of the patient’s acid–base and electrolyte status, as citrate metabolism can lead to metabolic alkalosis, hypocalcemia, and hypernatremia. However, these effects can be diminished by infusing calcium into the circuit and using a low bicarbonate dialysate or chloride based intravenous fluids. Using a higher chloride citrate solution can also blunt the alkalotic effect. Hypernatremia can be prevented by using lower sodium dialysate or appropriate replacement fluids.

A recent meta-analysis published in 2022 compared the efficacy of citrate vs. heparin anticoagulation in critically ill patients on undergoing CRRT [10]. The study noted no significant difference in mortality, metabolic alkalosis, and circuit loss between the two groups. It did note that the citrate group had the advantage of an overall longer filter life and significantly lower risk of bleeding and heparin-induced thrombocytopenia. As such, RCA was deemed to have priority for CRRT in critically ill patients (Table 3).

Anticoagulation method	Mechanism	Advantages	Disadvantages
Unfractionated heparin	Binds to antithrombin III, inhibits thrombin and factor Xa	Widely available, reversible, familiar dosing	Increased bleeding risk, requires monitoring, heparin-induced thrombocytopenia
Low molecular weight heparin	Binds to antithrombin III, inhibits factor Xa more than thrombin	Longer half-life, predictable dosing	Risk of bleeding, accumulation in renal dysfunction, expensive
Regional citrate anticoagulation	Citrate infused pre-filter, calcium replacement post-filter	Reduced bleeding risk, no systemic anticoagulation required	Need for calcium monitoring, risk of metabolic derangements

Table 3.

Comparing major types of anticoagulation in CRRT [10].

6.4 Monitoring clotting function and dosing

It is essential to monitor the clotting function of the blood during CRRT and adjust the anticoagulant dosing accordingly.

During CRRT, the clotting function of the blood is monitored using either the aPTT or the ACT. The aPTT measures the time it takes for clotting to occur in a blood sample after the addition of an activator, while the ACT measures the time it takes for clotting to occur in a blood sample after the addition of an activator and a contact activator. Both tests are used to monitor the effectiveness of UFH anticoagulation.

The dose of UFH for CRRT is typically titrated to achieve a target aPTT or ACT. The initial dose is usually 500–1000 units per hour, with adjustments made every 4–6 hours based on the patient’s clotting function. LMWH dosing is based on the patient’s weight, with dalteparin typically given as a subcutaneous injection at a dose of 5000 units every 12 hours. There is insufficient data to currently recommend for the use of LMWH in CRRT circuit.

RCA dosing is based on the infusion rate of citrate, which is typically started at a rate of 4–6 mmol/min and adjusted based on the patient’s ionized calcium levels (iCa). Goal is to maintain iCa between 1 and 1.4 mg/dl (0.25–0.35 mmol/l).

6.5 Complications

Despite appropriate anticoagulant dosing and monitoring, complications can still occur during CRRT. One of the main complications of CRRT is circuit clotting, which can lead to decreased filter life and increased risk of bleeding. Other complications include bleeding from anticoagulation, metabolic derangements from RCA, and hypotension from the fluid removal during CRRT.

6.6 Conclusion

The choice of anticoagulant for CRRT is a complex one that should be made on a case-by-case basis. There is no single “best” anticoagulant, and the best choice will vary depending on the patient’s individual circumstances.

7. Optimal RRT prescription, initiation timing, drug dosing, and lab monitoring, complications of RRT

7.1 Optimal RRT modality

The choice of RRT depends on the institution, resources available, nurses training and patient’s clinical status. Either IHD, PD, PIKRT such as SLED or CRRT can be used in ICU. CRRT tends to be the preferred modality in most ICUs. Given, CRRT does not require blood flow rates as high as IHD, CRRT tends to be the preferred modality for hemodynamically unstable patients. However, there is not any evidence that supports one modality over another.

A systematic review and meta-analysis published in 2021 (by Ye et al.) [11] compared different modalities of RRT through 31 randomized controlled trials. The review concluded that there was no overall difference in mortality between CRRT and IHD. However, CRRT was noted to increase renal recovery compared to IHD. Slow-efficiency extended dialysis with hemofiltration may be the most effective intervention at reducing mortality, but more research is needed. PD is associated with good efficacy and the least number of complications but may not be practical in all settings. ICU clinicians should feel comfortable that the differences between CRRT, IHD, slow efficiency extended dialysis, and PD are small, and any of these modalities is a reasonable option to employ in critically ill patients.

SLED can be useful if the patient requires multiple procedures that would interrupt CRRT, Since CRRT needs to be operating with as few interruptions as possible over 24 hours. Some institutions use SLED to transition patients from CRRT to standard IHD as hemodynamic stability improves.

One meta-analysis found no statistically significant difference between SLED and CRRT regarding patient-centered outcomes such as mortality, kidney function, recovery, dialysis dependence, length of stay in ICU, and fluid rate. SLED is also generally less expensive to administer and has similar safety for patients as CRRT.

Timing of onset: Multiple trials have compared the timing of RRT initiation in critically ill patients with AKI. Early RRT initiation (within 12 hours of identification) was not associated with improved outcomes and may be associated with increased risk of adverse events. Delayed RRT initiation (until indications develop) is preferred [12], but there are likely to be limits to how long RRT can be safely delayed. The optimal timing of RRT initiation is still unknown.

• The STARRT-AKI trial [13] found no difference in mortality at 90 days between patients who received early RRT and those who received delayed RRT. However, patients who received early KRT were more likely to remain RRT-dependent at 90 days and to require rehospitalization.

• A meta-analysis of nine studies [14] found no difference in mortality at 28, 60, or 90 days between patients who received early RRT and those who received delayed RRT.

• The AKIKI-2 trial [15] found that mortality was higher in patients who had RRT deferred until an urgent indication developed or the BUN exceeded 140 mg/dL, but the difference was not statistically significant.

Based on the available evidence, delayed RRT initiation is preferred in critically ill patients with AKI. However, the optimal timing of RRT initiation is still unknown and may vary depending on individual patient characteristics.

Session length: Session length depends on the modality of dialysis and patients’ ability to tolerate it. IHD is about 3–4 hours 2–3 times a week. PIKRT is 3 times a week but for 8–16 hours a day. CRRT is optimally applied for 24 hours a day.

Dialysate flow rate: The flow rate ranges from 100 to 400 ml/min. The dialysate flow rate is adjusted for the anticipated duration of the session. There is a finite amount of dialysate volume per session, based on how much the machine can accommodate. If the session is needed to last more than 8 hours for example, a lower flow rate may be needed. The dialysis flow rates for CRRT and PIKRT are lower than IHD 100–200 ml/min compared to IHD 300-400 ml/min.

CRRT dialysate dosing: The ‘Randomized Evaluation of Normal versus Augmented Level of RRT’ (RENAL) trial [16] and the ‘Acute Renal Failure Trial Network’ (ATN) [17] trials were two large clinical trials that evaluated the higher intensity (40 or 35 cc/kg/h) vs. lower intensity (25 or 20 cc/kg/h) dosing of CRRT. There was no difference found between lower intensity vs. higher intensity groups. Lower intensity dosing is currently recommended.

Ultrafiltration rate: The rate is determined by hemodynamic stability and urgency to remove excess fluid. With hemodynamically unstable patients, UF of 50 ml/h is a good starting place and can increase over time, However, if a patient is severely volume overloaded and can tolerate higher volume removal, a much higher ultra filtration rate can be targeted. For IHD, multiple liters of fluid negativity per session can be targeted based on hemodynamic stability.

Blood flow: The highest blood flow that the catheter will allow is used. It is usually initiated at100mL/min for CRRT and gradually increased to 200 cc/min. The higher the blood flow, the less likely a clot forms in the extracorporeal circuit. IHD can be initiated at 300–400 ml/min.

Drug Dosing: Volume of distribution, Vd and protein binding determine the effectiveness of a drug for a patient on CRRT 24 hours a day. Ideally, an ICU pharmacist should help dose medications for patients on CRRT 24 hours a day. If a drug is less than 2000 Da in weight, it might be readily removed on CRRT. Such drugs may need a higher dosing than usual dosing. The higher the protein bound content, the lesser the likelihood the drug will be cleared during CRRT. If a patient is volume overloaded, the higher Vd should be accounted for compared to ideal body weight and drug should be dosed accordingly. When possible and where available, follow plasma concentrations of drugs to achieve therapeutic levels. If a patient is on intermittent dialysis, it may be possible to dose a drug whose clearance may be affected by dialysis outside the dialytic time.

Complications: The major complications Include hypotension and abnormalities in electrolytes, albumin, calcium, and phosphate. As far as hypotension, PIKRT or SLED is well tolerated. Like CRRT, the slow blood flow rates and low UF allows hemodynamically unstable patients to tolerate it well. Hypophosphatemia only occurs with prolonged or frequent PIKRT and requires phosphate supplementation.

It is typically recommended that electrolytes and acid–base status be monitored every 6–12 hours initially for CRRT. Should the patient remain stable with minimal electrolyte changes after 24–48 hours, lab monitoring frequency can be further spaced to every 12–24 hours.

In recent years, there have been some updates in CRRT monitoring technology, aimed at improving the accuracy and efficiency of the process. For example, newer CRRT machines now incorporate advanced sensors and algorithms that can detect changes in blood flow and pressure, helping to prevent clotting and other complications.

Another recent development is the use of electronic medical records (EMRs) and data analytics tools to track patient outcomes and identify potential areas for improvement. This approach has been shown to reduce errors and improve overall quality of care in CRRT patients.