© Borgis - New Medicine 3/2010, s. 102-106
*László Medve1, Emil Préda1, Tibor Gondos2
The practice of renal replacement therapy in the intensive care unit
1Dr. Kenessey Albert Hospital, Department of Anesthesiology and Intensive Care Medicine, Balassagyarmat
Head: Dr. Szabó Géza, General Director
2Semmelweis University, Faculty of Health Science, Department of Oxyology and Emergency Care, Budapest
Head: Prof. Dr. Mészáros Judit, Dean of Faculty
Little information is available regarding current practice in renal replacement therapy (RRT) for the treatment of acute kidney injury (AKI) and the possible clinical effect of practice variation. Over the last three decades the treatment options for patients with AKI requiring renal replacement therapy (RRT) have expanded from basic acute peritoneal dialysis and intermittent hemodialysis (IHD), to now include a variety of continuous modalities (CRRT), ranging from hemofiltration to dialysis and/or hemodiafiltration, and a variety of hybrid therapies, variously described as extended daily dialysis and/or hemodiafiltration. There is also disagreement on clinical practice for RRT including the best timing to start, vascular access, anti-coagulation, membranes, equipment and finally, if continuous or intermittent techniques should be preferred. This study surveyed the availability and current practice of renal replacement therapy in adult general intensive care units.
Introduction. After having learned the theoretical basis of renal replacement therapy (RRT) and after having established the objective conditions and appropriate environment, acute RRT may be initiated in the ICU. However, during the practical application of the chosen treatment modality, problems still can emerge. To solve these problems it is necessary to assess and manage practical issues arising during RRT.
Hemodialysis (HD): primarily diffusion-based treatment modality, where the water and dissolved substances are transported through a semipermeable membrane to the dialysis solution.
Hemofiltration (HF): primarily based on convective transport, where water and dissolved substances are transported through a semipermeable membrane. Substitution fluid must be administered in order to maintain liquid balance.
Hemodiafiltration (HDF): a method that combines high ultrafiltration rate and diffusion through a high permeability membrane. In other words, the method combines the benefits of hemodialysis and hemofiltration. The blood and the dialysis solution flow in opposite directions in the hemodialysis filter, but at the same time ultrafiltration takes place for fluid removal purposes. Substitution fluid should be given to ensure water balance.
Modality of RRT
The management of acute kidney injury (AKI) with renal support includes peritoneal dialysis, intermittent dialysis and continuous renal replacement techniques (1-4) (tab. 1).
Table 1. The management of acute kidney injury (AKI) with renal support.
|Peritoneal dialysis||Intermittent treatments||Continuous treatment|
|Every second day||Veno-venous hemofiltration|
|Every day||Veno-venous hemodialysis|
|Prolonged daily treatment||Veno-venous hemodiafiltration|
|New therapy guidelines|| |
|Continuous low efficiency hemodialysis||"High flux" dialysis|
|High volume hemofiltration|
Acute peritoneal dialysis in developing countries remains an important form of treatment, but nowadays there are other modern procedures to be considered.
Intermittent hemodialysis treatments (IHD)
Daily Intermittent Hemodialysis:
– 4-6 hours per day of hemodialysis treatment
– blood flow from 300 to 350 ml/min
– target urea reduction ratio of at least 0.65
Extended Daily Dialysis
– 6-10 hours daily treatment
Alternate Daily Hemodialysis is performed every other day
– Typically 3-4 times a week with at least 4 hours treatment at a time.
Continuous Renal Replacement Therapy (CRRT)
Continuous Renal Replacement Therapy is carried out continuously (24 hours per day) using a veno-venous catheter in which the blood flow is significantly lower than during IHD. The most commonly used modalities of CRRT are continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration (CVVHDF). CRRT has a slower solute clearance compared to IHD, but the 24-hour full-clearance balance is higher than that of IHD, particularly for high molecular weight substances, e.g. cytokines. During CRRT the fluid elimination is much slower, and the treatment usually requires continuous anticoagulation with the potential risk of bleeding. The extracorporeal system also removes other substances with the possible risk of electrolyte and nutrient imbalance and antibiotic concentration below therapeutic levels (5).
Continuous veno-venous hemofiltration (CVVH)
– ultrafiltrate is produced, which must be replaced with a substitution solution,
– the removal of excess ultrafiltrate may result in volume loss of the patient,
– the solute removal takes place through convective transport.
Continuous veno-venous hemodialysis (CVVHD)
– the dialysis solution flows opposite to the blood in the dialysis filter,
– the speed of blood flow is 100-200 ml/min,
– speed of the dialysis solution is 1-2 l/h,
– fluid administration is not routine,
– solute removal takes place through diffusion.
Continuous veno-venous hemodiafiltration (CVVHDF)
– the dialysis solution flows opposite to the blood in the dialysis filter,
– speed of blood flow is 100-200 ml/min,
– speed of the dialysis solution is 1-2 l/h,
– the ultrafiltration rate should be optimized in accordance with the volume loss and the convective transport of dissolved substances,
– the fluid can be replaced with substitution solution,
– solute removal takes place simultaneously by convection and diffusion.
New therapeutic procedures (6-9)
Long-term, low-efficiency dialysis (Slow Low Efficiency Dialysis)
– blood flow 150 to 200 ml/min,
– dialysis flow 100 to 200 ml/min,
– treatment duration: 10-24 hours.
Continuous High Flux Dialysis (CAVHFD/CVVHFD)
– using high-permeability membrane in which the blood flows opposite to the dialysis solution,
– the production of ultrafiltered substance is controlled by a blood pump,
– it is important to balance between filtration and back-filtration: the ultrafiltrate is produced in the proximal part of the filter, while, because the back-filtration occurs in the distal part, there is no need for substitution fluid.
Continuous High Volume Hemofiltration (HVCVVH)
– a form of CVVH in which the hemofilter surface is large; therefore it is suitable to achieve> 35 ml/kg/h ultrafiltration rate.
The acute renal replacement protocol
Vascular access selection
Intermittent techniques require high blood flow (250-400 ml/min); the continuous techniques need lower blood flow (150-200 ml/min).
In renal replacement, the venous catheterization possibilities include the subclavian vein, the internal jugular vein and the femoral vein (10-14). The optimal input depends on the risk of thrombosis, the risk of infection, the insertion and the suitability of simpler sets. The catheter insertion depends on the patient (status of blood vessels, coagulation status), and the physician's experience. In general, the femoral vein is the fastest way to insert a central cannula, and may be best for bedridden, ventilated patients, or for patients with central nervous system trauma. The catheter length should be at least 25-30 cm and it usually should not be left in place for more than 2 weeks. The main risk of puncturing the subclavian vein is the possibility of venous stenosis/thrombosis of the efferent blood vessels. That is why the use of the subclavian vein is recommended just as a second option.
Recently, jugular vein puncture became favored. The main risk is infection, especially because of tracheostoma, and the proximity of the ear.
Many clinicians avoid the use of the subclavian vein, because of the risk of late stenosis, which can reach 50%. In contrast, late stenosis does not occur after internal jugular vein puncture: Altogether, the complication after using the internal jugular vein is around 10%, while after using the subclavian vein the complication rate is 19.6% (11).
However, when using the jugular vein we must take into consideration a higher risk of bleeding and thrombosis, compared to the use of the femoral vein.
When deciding the insertion site, most clinicians do not take the risk of infection into consideration, although after using the femoral catheter, infection is often observed. Special attention must always be paid to maximally comply with rules of hygiene.
In double lumen hemodialysis catheters the output and input blood gates are relatively close to each other and a certain amount of filtered blood is recirculated into the extracorporeal system. In order to reduce the recirculation, the most important issue is the proper positioning of the catheter. It is generally expected that, if a femoral catheter is used, then the tip of it should be in the inferior cava vein. For the other two inputs (internal jugular and subclavian vein) the best catheter position for the tip of the catheter is in the right atrium or the cava/atrium opening.
With the help of ultrasound we can enhance the security of the procedure and reduce the frequency of complications.
Choosing the treatment modality
In terms of clinically relevant outputs (mortality, admission to the ICU, hospital stay, mechanical ventilation, recovery of renal function), the available randomized controlled studies do not show a clear difference between continuous and intermittent therapy (8, 9).
In everyday practice, continuous treatment is recommended for hemodynamically unstable cases, and for patients who need persistent removal of fluid and toxic materials because of their underlying medical condition (6, 7).
Regarding removal of low molecular weight substances, continuous convection (CVVH) and diffusion (CVVHD)-based techniques appear comparable. Although by using convection the clearance of medium and high molecular weight substances is higher, this does not appear to provide clinical benefit.
Dialysis membrane selection
Considering the membrane structure, there are two basic types of membranes: the blood flows either along surface forming fibers (holofiber) or along membrane sheets/tubes (parallel plate).
The main consideration in selecting the filter/membrane is its property to remove low molecular weight materials, as well as medium/high molecular weight materials, filter/membrane properties and biocompatibility.
For removal of low molecular weight substances, beside conventional flow conditions (≤ 2 l/hour), the flow rate itself is crucial. For removal of medium/high molecular weight substances, not only the flow conditions are important, but also the hydraulic permeability and adsorption capacities of the membrane. The hemofilter and hemodialyzer must be selected according to the treatment modalities. Both types of membrane are appropriate (15).
The effectiveness of the membranes during treatment diminishes with time; therefore it will be necessary to replace them at certain intervals. Unfortunately, there is no sure way to monitor the operation and status of the membranes (tab. 2).
Table 2. Indicators of membrane effectiveness.
|Indicators of membrane effectiveness|
|Transmembrane pressure (TMP)||120-150 mmHg|
|Urea sieving coefficient||> 0.6 (CVVH)|
|Urea leverage ratio||> 0.6 (CVVHD, CVVHDF)|
|Filtering fraction||< 0.2 (CVVH)|
With the use of each membrane it should be taken into account that after 50 hours some hemolysis may develop. The period of use for a membrane depends on the manufacturer's recommendations and local infection control. In everyday practice, without anticoagulation treatment, the membranes must be changed every 24 hours.
Selection and application of substitution and dialysis fluid
The composition of dialysis and/or substitution fluid and the method of application is an important part of the hemodialysis strategy. The type of buffer used is an important issue in the literature, but there are few data about the advantages of using various components (regarding homeostasis, bacteriological aspects). There is a general consensus that the solution should contain an appropriate concentration of buffer and electrolytes, so that it conforms to physiological levels and can be adapted to the deficit and/or surplus in the body. In most cases, the substitution solution should contain physiological concentrations of electrolytes, with the exception of protein-bound ones (17).
A question yet to be decided is whether the liquid given during predilution (before the filter) or post dilution (after the filter) is effective as a treatment. This is a matter to be considered in each individual case.
By applying the predilution, an appropriate ultrafiltration rate can be achieved. This is important during HVCVVH (continuous high volume veno-venous hemofiltration) treatment. The use of predilution can reduce the frequency of filter clotting. The predilution can be combined with postdilution, especially if the maximum achieved blood flow controls the extracorporeal clearance rate.
During RRT, both lactate and bicarbonate can be used in the substitution and/or dialysis fluids. Lactate-based solutions should be avoided in patients with lactic acidosis or lactate intolerance. The classic sign is that the serum lactate level rises above 5 mmol/L during continuous treatments with lactate-based solutions. Lactate-based buffer may increase the acidosis during CRRT in patients with liver failure; therefore, in these patients, careful monitoring of the acid-base status is essential (16).
Lactate is an effective buffer in most patients treated with CRRT. Bicarbonate is preferred in lactic acidosis, hepatic failure, and high-volume hemofiltration.
If citrate is used as an anticoagulant, there is no need for another buffer, but the blood pH should be monitored.
During CRRT, the high volume turnover can reduce the body temperature. Despite the recommendation that temperatures below 35°C need to be avoided, according to the available data there is no evidence for the necessity of heating the CRRT fluid (19, 20).
If systemic anticoagulation is not justified, regional citrate anticoagulation is preferred. Heparin-protamine regional anticoagulation is not recommended because of protamine accumulation in ARF.
In the case of heparin-induced thrombocytopenia (HIT), the administration of non-fractionated or low molecular weight heparin should be stopped. Citrate should not be used for anticoagulation of extracorporeal circuits or to provide systemic thrombosis prophylaxis. Danaparoid (0.25-0.35 anti-Xa U/ml) may be considered if cross-reactivity with heparin-dependent antibodies is excluded (23). Fondaparin, bivalirudin, argatroban, dermatan sulfate or nafamostat could be considered as alternative options if the monitoring is resolved.
If there is increased risk of bleeding, regional citrate should be used. Treatment without anticoagulation may be considered, especially in serious coagulopathies (21).
If there is an increased clotting tendency, the use of unfractionated and low molecular weight heparin should be complemented with prostaglandins.
Controlling the efficiency and safety of the anticoagulant includes the monitoring of anticoagulant effects, the filter efficiency, the lifetime of the extracorporeal system and the possible complications. The anticoagulant effect of unfractionated heparin is measured in the post-filter blood by monitoring the activated clotting time (ACT), or systemic activated partial thromboplastin time (aPTT). The level of small molecular weight heparin and synthetic heparin may be measured by the activity of factor Xa. When using regional citrate, we need to control in parallel the level of postfilter ACT, the level of ionized calcium and the systemic calcium concentration. Maintaining their specific targets ensures the operation of the filter without increasing the possibility of complications (24).
The filter's lifetime is an important factor in the measurement of efficacy, because in many centers it is used for the assessment of anticoagulation. The filter efficacy can be followed by measuring the ultrafiltration rate, if it is not pump-controlled.
The transmembrane pressure is also suitable for assessing the interoperability of the membrane (22), which reduces with filter clotting. This can be avoided by using citrate and, to a lesser extent, prostacyclin. The direct measurement of pre- and postfilter pressure is not predictive of assessing the filter's clotting.
The complications of the various anticoagulants are different. The main complication is bleeding; therefore, every case of occult bleeding should be monitored. Systemic heparinization is the most widely used method, in which the bleeding rate is 10-50%, and the rate of development of HIT is 5-10%, depending on the type of heparin.
Not only the diagnosis of AKI and its conservative therapy, but also renal support treatment is an integral part of managing patients with AKI in the ICU. RRT is a continuous 24-hour treatment modality in the ICU, just like fluid therapy, circulation support or mechanical ventilation. In terms of indicating and carrying out renal support treatment the reference place is the ICU with its trained personnel, evidently also involving the support of fellow disciplines.
AKI Acute kidney injury
CRRT Continuous renal replacement therapy
CVVH Continuous veno-venous hemofiltration
CVVHD Continuous veno-venous hemodialysis
CVVHDF Continuous veno-venous hemodiafiltration
EDD Extended daily dialysis
HVHF High volume hemofiltration
HVCVVH High volume continuous veno-venous hemofiltration
IHD Intermittent hemodialysis
ICU Intensive care unit
RRT Renal replacement therapy
1. Bellomo R, Ronco C and Mehta R: Nomenclature for continuous renal replacement therapies. Am J Kidney Dis 1996; 28: S2-S7. 2. Pannun et al.: Renal replacement therapy in patients with acute renal failure. JAMA 2008; 299(7): 793-808. 3. Ronco C, Bellomo R: Basic mechanisms and definitions for continuous renal replacement therapies. Int J Artificial Organs 1996; 19: 95-99. 4. Paganini EP: Continuous replacement modalities in acute renal dysfunction. [In:] Paganini EP, ed. Acute continuous renal replacement therapy. Boston: Martinus Nijhoff 1986; 7-42. 5. Locatelli F, Di Filippo S, Manzoni C: Removal of small and middle molecules by convective techniques. Nephrol Dial Transplant 2000; 15(Suppl. 2): 37-44. 6. Ronco C et al.: Effects of different doses in continuous veno-venous hemofiltration on outcomes of acute renal failure: a prospective randomized trial. Lancet 2000; 355: 26-30. 7. Ronco C: Textbook of Critical Care 2005. 8. Pannun et al.: Renal replacement therapy in patients with acute renal failure. JAMA 2008; 299(7): 793-808. 9. VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. NEJM 2008. May 20. 10. Oliver MJ et al.: Risk of bacteremia from temporary catheters by site of insertion and duration of use: a prospective study. Kidney Int 2000; 58: 2543-5. 11. Canaud B et al.: Temporary vascular access for extracorporeal therapies. Ther Apher 2000; 4: 249-55. 12. Abidi SM et al.: Factors influencing function of temporary dialysis catheters. Clin Nephrol 2000 Mar; 53(3): 199-205. 13. NKF-K/DOQI clinical practice guidelines for vascular access update 2000. American Journal Kidney Diseases 2001; 37(Suppl. 1): S139-S181. 14. Parienti JJ et al.: Femoral vs. jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy: a randomized controlled trial. JAMA 2008; 299: 2413-22. 15. Bambauer R et al.: New surface treatment technologies for catheters used for extracorporeal detoxification. Dial Transplant 1995; 24: 228-38. 16. Thomas AN et al.: Comparison of lactate and bicarbonate buffered hemofiltration fluids: use in critically ill patients. Nephrol Dial Transplant 1997; 12: 1212-1217. 17. Heering P et al.: Acid-base balance and substitution fluid during continuous hemofiltration. Kidney Int 1999; 56(Suppl. 72): S37-40. 18. Brunet S et al.: Diffusive and convective solute clearances during continuous renal replacement therapy at various dialysate and ultrafiltration flow rates. Am J Kidney Dis 1999; 34: 486-492. 19. Matamis D et al.: Influence of continuous hemofiltration-related hypothermia on hemodynamic variables and gas exchange in septic patients. Intensive-Care Med 1994; 20: 431-436. 20. Yagi N et al.: Cooling effect of continuous renal replacement therapy in critically ill patients. Am J Kidney Dis 1998; 32: 1023-1030. 21. Sanders PW, Taylor H, Curtis JJ: Hemodialysis without anticoagulation. American Journal of Kidney Diseases 1985; 5: 32-5. 22. Holt AW et al.: Continuous renal replacement therapy in critically ill patients: monitoring circuit function. Anaesth Intensive Care 1996 Aug; 24(4): 423-9. 23. Acostamadiedo JM, Iyer UG, Owen J: Danaparoid sodium. Expert Opin Pharmacother 2000; 1: 803-814. 24. Michael Joannidis1 and Heleen M Oudemans-van Straaten: Clinical review: Patency of the circuit in continuous renal replacement therapy. Critical Care 2007; 11: 218 (doi:10.1186/cc5937).