Basic principles of renal replacement therapy

Acute kidney injury (AKI) is a common complication in critically ill patients admitted to the intensive care unit (ICU). Epidemiologic data suggest that over 50% of ICU patients suffer from AKI, and up to 13.5% will be treated with renal replacement therapy (RRT). Change in patient characteristics, with admission of older patients with more comorbidities such as diabetes, cardiovascular disease, and hypertension, resulted over the last decade in a marked increase of the proportion of patients treated with RRT. ^, RRT has therefore become an essential and often used treatment option for ICU patients, involving a spectrum of treatment modalities, with various advantages and disadvantages depending on the situation. RRT is most often delivered via extracorporeal techniques, but the COVID-19 pandemic caused renewed interest in peritoneal dialysis (PD), a technique using the peritoneum of the patient as a semipermeable exchange membrane.

Technical aspects of RRT

Extracorporeal techniques can be done with different modalities ( Table 38.1 ). These are named according to the duration of RRT and the technique used for exchange of solutes and water: diffusion or convection.

TABLE 38.1

Renal Replacement Therapy Modalities

Modality	Abbreviation	Treatment Duration (per day)	Blood Flow (mL/h)	Dialysate Flow (mL/min)
Intermittent hemodialysis	IHD	2–4 h	200–450
Hybrid techniques Slow low-efficiency daily dialysis Extended daily dialysis Prolonged intermittent renal replacement therapy	SLEDD EDD PIRRT	6–12 h	150–200	One and a half times blood flow
Continuous renal replacement therapy Continuous venovenous hemofiltration Continuous venovenous hemodialysis Continuous venovenous hemodiafiltration	CRRT CVVH CVVHD CVVHDF	24 h	100–250
Peritoneal dialysis Manual exchanges Automated PD (cycler)	PD CAPD APD	Solution: dextrose 1.5% or glucose 1.36% to start, higher glucose concentration according to ultrafiltration needs Fill volume 1500–2000 mL Dwell time per exchange: 2 h, consider change to 4 h once acidosis, pulmonary edema, and hyperkalemia are resolved

Diffusion and convection

Exchange of waste products over the semipermeable membrane can be via diffusion (hemodialysis) or convection (hemofiltration) ( Fig. 38.1 ). In diffusion, blood and dialysate flow countercurrent on both sides of the semipermeable membrane of the hemofilter. The driving force that moves solutes over the semipermeable membrane is the solute concentration gradient. Uremic toxins such as blood urea nitrogen and creatinine will have high blood concentrations and are absent in the dialysate. Other factors that determine the movement of solutes from blood to dialysate are the diffusion coefficient of the membrane, its thickness, and its surface area. Diffusion is very efficient in the removal of small molecules such as potassium, ammonium, and creatinine (<500 Da); it is less efficient in the removal of larger solutes.

Fig. 38.1, Diffusion (as in hemodialysis) and convection (as in hemofiltration). R, Replacement fluid; V, venous blood prefilter and postfilter.

In hemofiltration, solutes and water are transported over the membrane by a difference in pressure between both sides of the membrane. Water and solutes are pressed from the blood compartment to the so-called effluent. The permeability coefficient of the membrane and the difference in pressure between both sides of the membrane determine the amount of fluid and solutes transported over the membrane. The effluent rate is controlled by a pump. Hemofiltration is more efficient for removal of larger molecules. In hemodiafiltration, both convection and diffusion are combined.

There are currently no data to suggest the superiority of diffusion over convection.

Duration of RRT

Intermittent hemodialysis (IHD) is a very efficient dialysis technique performed during a 3- to 4-hour period; continuous renal replacement therapy (CRRT) is less efficient, but done 24 hours a day; and hybrid techniques, alternatively termed sustained low-efficiency daily dialysis or extended daily dialysis (SLEDD or EDD), have intermediate efficacy and are used 6–12 hours per day. ^,

Intermittent and hybrid therapies will be performed with the use of dialysis machines that are also used for chronic dialysis patients. These monitors typically have more complicated interfaces and are therefore often managed by dialysis nurses. CRRT is most often performed with specifically designed monitors with a relatively easy interface and are managed by ICU nurses. Some centers also use these RRT machines for hybrid therapy.

Specifics aspects of a CRRT circuit

Fig. 38.2 shows the different aspects of CRRT performed as continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF).

Fig. 38.2, Schematic representation and definitions of the different continuous renal replacement therapies according to standard nomenclature. Functional capabilities are described. A, Artery; D, dialysate; K, clearance; Pf, plasma filtration rate; Qb, arterial flow; Qd, dialysate flow; Qf, ultrafiltration rate; UF, ultrafiltrate; UFc, ultrafiltrate control pump; V, vein.

Dose of RRT

The dose of CRRT is by convention expressed as the clearance of urea, a small molecule that both in hemodialysis and hemofiltration is not retained by the membrane. The effluent rate—the volume of fluid produced by hemofiltration and/or hemodialysis—therefore equals the clearance of urea, and when corrected for body weight, can be used to express the dose of CRRT: dose of CRRT = effluent rate per hour per kg body weight (mL/kg/h). For a desired dose of 25 mL/kg/h for a 60-kg patient, the effluent rate will be 25 × 60 = 1500 mL/h. This effluent needs to be partly or completely replaced by a replacement fluid; otherwise, fluid losses will be too high. The amount of effluent that is replaced will determine the fluid balance of the patient. This replacement fluid can be given prefilter (predilution), postfilter (postdilution), or in a combination of both. When given in postdilution mode, blood will concentrate while passing through the capillaries of the hemofilter. This may lead to clogging (partial clotting) and clotting of the capillaries, leading to decreased efficacy because fewer capillaries are available. To prevent this, a filtration fraction—the proportion of effluent over plasma flow—of less than 25% is advised. The filtration fraction is indicated on the dashboard of present-day CRRT machines.

In CRRT, the delivered dose should be 20–25 mL/kg/h of effluent. Two large prospective randomized studies compared this dose to a higher dose and found that outcomes were similar. ^, Treatment interruptions often lead to a lower delivered dialysis dose. Therefore it is advised to prescribe a dose of 25–30 mL/kg/h.

In intermittent RRT, the minimum delivered dose of dialysis should be three sessions of at least 3 hours per week, with a blood flow of >200 mL/min and a dialysate flow of >500 mL.

Anticoagulation

During RRT, the patient’s blood is purified by circulating it through an extracorporeal circuit containing a hemodialyzer, consisting of about 10,000 semipermeable capillary fibers. Disordered blood flow and contact of the blood with the bioincompatible material of the fibers activate the coagulation cascade, leading to clotting and subsequent blocking of the capillary fibers. This results in a reduction of the efficiency of the dialysis procedure, as fewer fibers remain available for solute exchange. When more pronounced, coagulation can even cause loss of extracorporeal blood volume by complete clotting of the extracorporeal circuit, so blood can no longer be returned to the patient. Anticoagulation for RRT should be tailored according to patient characteristics and the modality chosen. Capturing the end result of the rebalanced hemostatic system in ICU patients with AKI is challenging, but new laboratory testing methods, including thromboelastography/ rotational thromboelastometry (TEG/ROTEM) and thrombin generation assays, potentially yield vital information. The first technique assesses development, strength, and dissolution of clots by viscoelastic testing and does not take long before providing results. It offers information on the contribution of both enzymatic and cellular components in whole blood. Thromboelastometry analysis progressively finds acceptance in the care of patients undergoing high-risk surgery. The second, thrombin generation (TG), mirrors a significant part of the overall hemostatic system, reflecting contributions of natural procoagulants and anticoagulants to hemostasis and the effect of drugs. Many semiautomated and fully automated assays are on the market today, although regrettably still lacking interlaboratory standardization.

Special attention is required for nonanticoagulant strategies to avoid coagulation of the circuit. Patients with a high hematocrit are at higher risk for clotting of the extracorporeal/dialysis circuit because of the higher viscosity of the blood. Blood products should be administered separate from RRT as much as possible. Prompt reaction to pump alarms is important, avoiding interruption of the blood flow. In this regard, well-functioning vascular access is fundamental. Circuits with a lot of blood-air contact because of the use of drip chambers are especially prone to clotting. There is no evidence pointing towards the efficacy of intermittently rinsing the circuit with saline flushes to prevent clotting.

No anticoagulation strategy

Several authors described large series of patients treated without any form of anticoagulation during RRT for AKI (in up to 50%–60%). ^, Especially in patients with coagulopathy, an acceptable treatment length can be reached even without anticoagulant. Risking circuit clotting—in the worst case implying the loss of approximately 200 mL of extracorporeal blood and eventually also the venous access—may be defensible in patients with high bleeding risk. Neither the effect of clogging on filter performance nor the consumption of coagulation factors in RRT without anticoagulation are well studied.

Unfractionated heparin (UFH)

Current guidelines suggest using UFH for intermittent RRT in patients without increased bleeding risk and in the case of contraindications for citrate in continuous RRT. It has a half-life between 0.5 and 3.0 hours in patients receiving dialysis. It has a rapid action time of approximately 3–5 minutes. UFH acts by potentiating thrombin and inhibiting activated factor Xa. A variety of infusion schemas exists, including single dose, repeated bolus, or continuous infusion. An example of a standard dosing regimen is a bolus of 500–1000 units at the start of treatment, followed by 500–750 units/h. Other authors suggest adapting the dose to the body weight, starting with a bolus of 10–20 units/kg/h, followed by a maintenance infusion of 10–20 units/kg/h that typically would be stopped 30 minutes before the end of treatment. UFH treatment needs to be individualized according to the clinical setting. It can be monitored with routine laboratory tests as activated partial thromboplastin time (aPTT) or activated coagulation time (ACT), but many centers move to anti–factor Xa assays for monitoring UFH because it reflects the anticoagulant activity more adequately, especially during inflammatory conditions. ^, Anti–factor Xa level–guided anticoagulation protocols yield important potential in decreasing filter clotting. If routine laboratory tests are used, typical anticoagulation targets in ICU patients are 1.5–2 times prolongation of the aPTT and 40% increase of ACT. If needed, UFH can be reversed with protamine. Heparin failure, resulting in clotting of the circuit, can be the result of antithrombin deficiency or UFH neutralization by binding to plasma proteins. During treatment, the thrombocyte count should be monitored, allowing timely detection of heparin-induced thrombocytopenia (HIT).

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here