This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Petroni, K. C. Articles by Cohen, N. H. Search for Related Content PubMed PubMed Citation Articles by Petroni, K. C. Articles by Cohen, N. H.

---

CRITICAL CARE AND TRAUMA

Continuous Renal Replacement Therapy: Anesthetic Implications

Kenneth C. Petroni, MD^*, and Neal H. Cohen, MD MPH, MS

*Department of Anesthesiology, Naval Medical Center San Diego, California; and Department of Anesthesia and Perioperative Care, University of California, San Francisco

Address correspondence and reprint requests to LCDR Kenneth C. Petroni, c/o Clinical Investigation Department (KCA), Naval Medical Center San Diego, 34800 Bob Wilson Dr., Ste. 5, San Diego, CA 92134-1005. Address e-mail to petronik{at}yahoo.com

	Introduction

Top Introduction Conclusion References

 
Renal dysfunction is a common problem for patients presenting for surgical procedures. Acute renal failure (ARF) occurs in 2%–5% of hospitalized patients (1); the incidence is likely to increase as the population ages. Many patients with underlying renal dysfunction require anesthesia and surgery, often for clinical problems unrelated to their renal disease. Renal failure complicates intraoperative management and contributes to perioperative morbidity and mortality (2). Fluid and electrolyte abnormalities associated with renal failure also complicate intraoperative management and postoperative care. Until recently, few interventions were available to facilitate management of the surgical patient with renal function abnormalities or intravascular volume overload, particularly in the postoperative period. Diuretic therapy is frequently used to improve urine output after surgery, but its use is often associated with significant fluid and electrolyte shifts, hypovolemia, and vital organ hypoperfusion. Dopamine has been used to improve renal blood flow and urine output but has not been demonstrated to prevent perioperative renal failure. Acute hemodialysis has also been initiated for patients who develop postoperative renal dysfunction, but it is often difficult to use because major fluid shifts are poorly tolerated in the early postoperative period by patients who have undergone a major surgical procedure. Continuous renal replacement therapy (CRRT) represents a relatively new group of treatments available for the management of patients with ARF, fluid overload, or metabolic instability. With the increasing use of CRRT, anesthesiologists will participate in the care of patients receiving these therapies and should therefore be familiar with the basic principles and potential applications. They should also consider the therapies as a potential treatment to facilitate the perioperative fluid and electrolyte management for selected patients. This review will define CRRT and describe the therapeutic options, define the clinical indications, and identify the issues that the anesthesiologist should consider when caring for the patient who requires renal replacement therapy.

Renal Replacement Therapies
Although the terminology may not be familiar to most anesthesiologists, renal replacement therapies are not new. The term is used to describe a spectrum of treatments that includes conventional intermittent hemodialysis (CIHD) and a wide variety of other therapies (Table 1).

Although CIHD is often used, it does have many shortcomings, particularly when used to treat the unstable perioperative or critically ill patient. CIHD may cause severe hemodynamic instability that often results in the inability to continue therapy or in incomplete fluid removal or dialysis. Hypotension is common during CIHD, particularly for the patient undergoing large intra- and extravascular fluid shifts. Some of the causes for a decrease in blood pressure during CIHD include changes in intravascular volume (preload), electrolyte changes, acid-base abnormalities, hemodynamic effects of buffering drugs, and impaired sympathetic response (4,5). The hypotension that accompanies acute dialysis often requires treatment with vasopressors or fluid resuscitation. In many cases the need for fluid resuscitation causes the already volume-overloaded patient to have a greater positive fluid balance after than before dialysis (6). Animal studies have also demonstrated an impaired ability of the kidney to autoregulate renal blood flow in ARF (7). Recurrent episodes of hypotension, as can occur with intermittent dialysis, can cause decreases in renal blood flow and worsen renal ischemia. The institution of any dialytic therapy, therefore, should be carefully monitored, and interventions should be made to maintain hemodynamic stability as much as possible to prevent further compromise in renal perfusion (8). Finally, CIHD requires dedicated personnel and equipment, which are not always available, particularly in the face of acute fluid overload or metabolic instability, and is not readily available for use in the operating room (OR).

Peritoneal Dialysis
Peritoneal dialysis (PD) is also a renal replacement therapy. For patients with chronic renal failure and relatively few coexisting morbidities, PD is simpler to institute than CIHD. It can be used intermittently or in a slower, more continuous fashion. However, PD is not a form of renal replacement therapy that can be used to manage ARF for most surgical patients. It is contraindicated for patients who have recently undergone abdominal surgery and for patients with any intraabdominal pathology, ileus, or peritonitis. It must be used with caution in patients with limited respiratory reserve, because the large volumes of peritoneal dialysate can compromise pulmonary function and gas exchange (8). PD is associated with other complications, including abdominal pain, protein loss, hyperglycemia, and infection (9).

CRRTs
A variety of alternative CRRTs have been developed to address many of the problems associated with CIHD and PD. Collectively, these modalities are referred to as CRRT. CRRT provides better metabolic control of azotemia than CIHD (10,11), improves fluid removal without compromising intravascular volume (10,12), and facilitates fluid and electrolyte management and nutritional support in critically ill patients (10,11). Because of its utility in the critically ill patient with ARF, CRRT has become a popular form of renal replacement therapy in Europe and Australia (13).

Definition: Common Features of CRRT
CRRT refers to any continuous mode of extracorporeal solute or fluid removal. A variety of renal replacement therapies are encompassed within the term CRRT. Common to all forms of CRRT is an extracorporeal circuit connected to the patient via an arterial or venous access catheter, or both. All CRRT circuits include a hemofilter with a semipermeable membrane. By connecting the hemofilter to the patient’s circulation, fluid can be removed from the patient on the basis of the hydrostatic pressure gradient across the filter. The rate of fluid removal is affected by either the patient’s arterial blood pressure (when an arterial cannula is used) or by the pressure generated with an extracorporeal pump (for venous cannulation techniques). The ultrafiltrate is composed of water as well as compounds with a molecular weight of up to approximately 20,000 Da (14).

Large volumes of ultrafiltrate can be removed with CRRT. To prevent volume depletion, fluid is replaced through the system to optimize intravascular volume and normalize electrolytes. The infusion rate and composition of the replacement fluid are variable and are dictated by the rate of ultrafiltrate formation, the rate of all other IV fluids administered to the patient, and the need for a positive or negative hourly fluid balance. In patients undergoing CRRT, bicarbonate is lost in the ultrafiltrate and by the neutralization of exogenous acids. Therefore, the replacement fluid is usually an isotonic, buffered electrolyte solution. The buffer used in the replacement fluid may be acetate, citrate, lactate, or bicarbonate. The use of citrate is becoming more commonplace because it may be used as both a buffer and an anticoagulant to help prevent hemodiafilter clotting (15).

In addition to allowing careful control over fluid balance with hemofiltration, CRRT can also be used as a form of dialytic therapy for patients with renal insufficiency. When dialysis is required, the volume of ultrafiltrate can be controlled as necessary to provide adequate uremic control. Alternatively, a dialysate can be run through the hemofilter in a countercurrent direction. The dialysate creates a concentration gradient across the hemofilter membrane, resulting in solute clearance by diffusion.

CRRT Nomenclature
Modes of CRRT are defined on the basis of the source of blood flow to the system, the location of blood return to the patient, and the therapy used (hemofiltration, dialysis, or both). As with any new technology, the nomenclature for CRRT is evolving. In an effort to standardize the terminology, a consensus conference was held at the 1995 International Conference of Continuous Renal Replacement Therapy (16), which defined the following modes of CRRT.

Continuous Arteriovenous Hemofiltration
Continuous arteriovenous renal replacement therapy includes CRRTs in which blood is removed from the patient through an arterial catheter and returned to the patient through a venous catheter. Flow through the hemofilter is dependent on the patient’s arterial blood pressure. If the blood pressure decreases, the amount of hemofiltration decreases. When used to remove ultrafiltrate and control fluid balance by adding replacement fluid alone, the therapy is termed continuous arteriovenous hemofiltration (CAVH). If the arteriovenous system is also used for dialysis by adding dialysate solution, the therapy is called continuous arteriovenous hemodialysis. If the patient undergoes both dialysis and fluid removal while receiving replacement fluids, the therapy is termed continuous arteriovenous hemodiafiltration (CAVHDF).

Continuous Venovenous Hemofiltration
Another form of CRRT requires venous access alone. A dual-lumen venous catheter is placed to allow aspiration of blood from the patient through a distal catheter lumen, transfer blood across the hemofilter, and return blood to the patient through the proximal catheter port. In this system, a pump is required to ensure a sufficient pressure gradient to facilitate hemofiltration. When ultrafiltrate volume is replaced, the method is termed continuous venovenous hemofiltration. When the patient undergoes continuous dialysis alone without net fluid removal or the use of a replacement fluid, the method is termed continuous venovenous hemodialysis. When the patient is dialyzed with fluid removal and receives replacement fluid, the therapy is named continuous venovenous hemodiafiltration. Continuous venovenous hemofiltration has become the most commonly used form of CRRT.

Slow Continuous Ultrafiltration
Slow continuous ultrafiltration (SCUF) is another form of CRRT not associated with fluid replacement. During SCUF therapy, the ultrafiltrate removal is controlled so that fluid removal is slow; with this therapy, fluid replacement is unnecessary. The treatment relies on equilibration of fluid across intravascular and extravascular spaces to prevent intravascular volume depletion. The primary purpose for SCUF is the management of refractory fluid overload in patients with or without renal failure. For example, SCUF is often used to treat the hemodilution and hypervolemia that accompany cardiopulmonary bypass (CPB) in pediatric patients.

Indications for CRRT
Renal Indications for CRRT
The most obvious indication for renal replacement therapy is ARF. CRRT can also be used to facilitate fluid clearance, correct electrolyte abnormalities, and manage metabolic acidosis (Table 2). CRRT provides a more stable hemodynamic profile than CIHD and minimizes the risks of infection associated with PD. Because CRRT is a slow, continuous form of therapy, treatment of renal failure and fluid and electrolyte abnormalities is possible without hemodynamic compromise. The therapy has been used very successfully to facilitate the management of a variety of surgical patients. van Bommel et al. (10) retrospectively reviewed 94 consecutive surgical intensive care unit (ICU) patients with ARF treated with either CAVHDF or CIHD. Despite being sicker and having more organ dysfunction, patients treated with CAVHDF had more hemodynamic stability and better control of fluid balance. Davenport et al. (17) studied the hemodynamic changes associated with CAVHDF and CIHD in patients with acute hepatic and renal failure. The patients treated with CIHD had significant decreases in mean arterial pressure, pulmonary artery occlusion pressure, cardiac index, and oxygen consumption, whereas patients undergoing CAVHDF had no significant hemodynamic changes.

Another important indication for CRRT is to facilitate nutritional replacement for malnourished or catabolic patients. In particular, for patients with ARF or fluid overload, nutritional support is a challenge. CRRT can be used to optimize nutritional support without causing further intravascular fluid overload. In an analysis of 234 critically ill patients, Bellomo et al. (11) showed that CRRT was more effective than CIHD in allowing continuous delivery of full nutritional support to patients with ARF. In a group of surgical patients with ARF, Bartlett et al. (20) demonstrated improved survival when CAVH was used to optimize fluid balance and allow early institution of full nutritional support.

Although CRRT has potential advantages and is safe when used to manage critically ill patients with ARF, it is still important to note that no prospective, randomized study has shown CRRT to improve patient survival when compared with CIHD. The two prospective, randomized studies comparing CRRT with IHD that have been performed showed no difference in hospital outcome. These studies have not been reported in peer-reviewed journals; they have been criticized for their poor methodology and design (21).

Nonrenal Indications for CRRT
CRRTs have also been used to manage a variety of clinical problems in patients with or without ARF. The nonrenal indications for CRRT include fluid overload, sepsis, congestive heart failure (22), and cerebral edema (23) (Table 2). Ossenkoppele et al. (24) first described the safe and effective management of fluid overload with CRRT in septic patients who were hemodynamically unstable and had ARF. Since that time, the use of CRRT to optimize fluid balance has become more commonplace, particularly in critically ill patients, in patients with end-stage liver disease, and, occasionally, during surgery to improve fluid balance. Because of its ability to favorably alter fluid status, CRRT also improves oxygenation and respiratory function in patients with acute respiratory distress syndrome (ARDS) (25,26) and pulmonary edema (27,28).

In human and animal studies, CRRT has been demonstrated to filter and remove cytokines, complement, and vasoactive mediators, including C3a, C5a, prostaglandin F_2a, tumor necrosis factor (TNF)-, interleukin (IL)-1, IL-6, IL-8, and myocardial depressant factor. In animal models of sepsis, CRRT improved hemodynamics, oxygenation, and survival (29–31). The ability of CRRT to effectively filter a variety of molecules from the circulation has stimulated many investigators to evaluate the effects of CRRT on the hemodynamics and outcome of patients with sepsis syndrome, multiple organ dysfunction syndrome, and ARDS. Although the most effective method of CRRT for sepsis has yet to be identified, it is likely that higher filtration rates, allowing for maximal filtration and removal of mediators, are beneficial. A recent study reported that a short period (4 h) of high-volume isovolemic hemofiltration dramatically improved hemodynamic variables in a subset of patients with profound circulatory failure secondary to septic shock (32). These findings are consistent with the improved survival rates found by Ronco et al. (33) when high-volume ultrafiltration was used in a mixed population of critically ill patients with ARF. Although CRRT has improved hemodynamics and survival in subsets of patients with sepsis syndrome, there are no randomized, controlled studies confirming its efficacy.

Anesthetic Implications of CRRT
Because of the demonstrated value and advantages of CRRT in the management of surgical patients, it is becoming a more commonly used therapy in the perioperative period. In some centers, CRRT is also used to optimize fluid and electrolyte management during surgery. This discussion will emphasize the anesthetic considerations for the patient who is receiving CRRT before surgery, the challenges associated with transitioning the patient to the OR, and the potential value of CRRT to facilitate intraoperative management.

Preoperative Assessment
The preoperative assessment of a patient receiving CRRT is challenging. Most patients receiving CRRT are critically ill and have multiple medical problems. Most are receiving mechanical ventilation, and many are hemodynamically unstable and require vasopressor or inotropic therapy. Because of the complexity of their medical problems, the usual preoperative emphasis on organ system disease is essential.

In addition to the usual considerations for management of the critically ill patient, the preoperative assessment of the patient receiving CRRT should focus on the indications for CRRT and the resulting physiologic derangements. The first question the anesthesiologist should answer is why the patient is receiving CRRT. From the previous discussion, it is clear that there are many indications for CRRT. Although it is likely that fluid management is an important perioperative issue, the patient may or may not have underlying ARF with all of its attendant anesthetic implications. Other indications for CRRT that would be of particular importance to the anesthesiologist are a history of hemodynamic instability and vasopressor dependence, sepsis, pulmonary edema or congestive heart failure, increased intracranial pressure, and electrolyte disorders such as hyperkalemia or metabolic acidosis. In many cases, the CRRT is being used to correct the metabolic sequelae of an underlying medical disorder (e.g., massive bicarbonate replacement in a patient with a severe metabolic acidosis). If the therapy is interrupted during transfer to the OR or during a surgical procedure, the metabolic abnormalities will return and may complicate intraoperative management. A thorough evaluation of intravascular volume, total fluid balance, cardiac function, and electrolytes is essential in planning intraoperative anesthetic and hemodynamic management.

The patient undergoing CRRT before surgery often has other significant medical problems that complicate intraoperative management and must be carefully evaluated. Patients with renal dysfunction often have coagulation abnormalities, including platelet dysfunction and thrombocytopenia. Despite these abnormalities, systemic anticoagulants are often required for patients receiving CRRT to prevent filter and circuit clotting. Anticoagulants, such as heparin, are most often administered before filtering, and when administered in this way they can have an unpredictable effect on systemic clotting mechanisms. Therefore, the potential for bleeding associated with the use of heparin must be considered. Heparin doses should be individualized and coagulation variables observed closely to minimize the likelihood of bleeding and to quickly detect other causes of systemic anticoagulation, such as disseminated intravascular coagulation or thrombocytopenia. For patients with a high risk of bleeding, including patients who are about to undergo a major surgical procedure, CRRT can be performed with regional anticoagulation or without any anticoagulation. Regional anticoagulation involves the prefilter infusion of either heparin or citrate and postfilter neutralization with either protamine or calcium. Palsson and Niles (34) retrospectively described the safe use of regional anticoagulation with citrate in a number of perioperative patients with a high risk of bleeding. Alternatively, Tan et al. (35) reported the safe and effective use of CRRT by use of prefilter replacement fluid without any pharmacologic anticoagulation in a small cohort of high-risk patients that included sev-eral in the immediate perioperative period. No matter how anticoagulation is managed during preoperative CRRT, the anesthesiologist should assess coagulation before proceeding with the procedure and should coordinate the anticoagulation strategy with the surgeon and physician managing the CRRT.

In addition to familiarity with the method of anticoagulation being used during CRRT and its effect on coagulation studies, the preoperative assessment should include a thorough assessment of the patient’s underlying coagulation status, including hemoglobin and hematocrit level, platelet count, prothrombin time, and partial prothrombin time. If the patient has any evidence of significant bleeding, for example, from IV line sites, incisions, and so on, qualitative assessment of clotting may also be warranted. Platelet dysfunction associated with ARF can be difficult to evaluate. Empiric administration of desmopressin or estrogen should be considered before elective surgery after all other causes have been excluded or treated. Finally, if systemic anticoagulation is being used, consideration should be given to using regional anticoagulation with citrate or to eliminating the use of anticoagulation altogether.

After completing a thorough preoperative assessment of the patient receiving CRRT, the anesthesiologist must determine when it is appropriate to discontinue the therapy before surgery and whether the surgery should be delayed until the patient is more stable. Additional intraoperative considerations include maintenance of fluid, electrolyte, and hemodynamic stability and whether to arrange for CRRT in the OR. For the majority of surgical procedures, the therapy can be safely discontinued before surgery and reinstituted afterward. For example, CRRT can almost always be stopped without significant consequence in the critically ill patient scheduled to undergo a tracheotomy, gastrostomy tube placement, minor wound debridement, or secondary closure. If CRRT is stop-ped, the system can be run in the bypass mode, in which the venous and arterial ends of the circuit are connected to each other. This mode allows continued flow through the circuit and hemofilter and obviates replacing the circuit after a short period of inactivity. Discontinuation of CRRT for a short period of time to undergo a procedure without significant fluid or electrolyte shifts is very unlikely to present any risk to the patient. The anesthesiologist must understand the reason for the CRRT and the benefits it has provided to patient management to plan fluid management and intraoperative care, although the consequences of discontinuing the therapy for a short time are usually insignificant.

The management of the patient scheduled for a major procedure is more difficult. The decision whether or not to continue CRRT during surgery requires a more thorough understanding of the underlying medical problems, the goals of CRRT, and the patient’s response to the treatment. Patients with severe underlying metabolic disorders (e.g., persistent hyperkalemia secondary to continuing rhabdomyolysis, or a persistent metabolic acidosis requiring constant bicarbonate therapy) may look relatively stable and well prepared for surgery because of the CRRT, rather than independently of it. In this circumstance, the patient scheduled for a long intraoperative procedure that is expected to be associated with large fluid shifts, hemodynamic instability, or both may be much easier to manage if CRRT is continued during surgery. Similarly, patients with ARF or increased intracranial pressure receiving CRRT for fluid management might also be candidates for intraoperative CRRT. Another clinical situation for which intraoperative CRRT has been used successfully is for patients undergoing liver transplantation or other major abdominal procedures during which major fluid shifts or electrolyte imbalances are anticipated.

Intraoperative Management
Most often CRRT will be discontinued before transport to the OR. The discontinuation of CRRT is not complicated, but it does require an understanding of the technique and the mechanics of the system. The CRRT filter and pumping system are separated from the access catheter, and the catheter is flushed with heparinized solution to maintain patency. For most patients, the CRRT access is best managed by capping the catheter to minimize the risk of dislodgement. When using the catheter for fluid administration or central venous pressure monitoring during surgery, blood should be aspirated from the catheter to remove the heparin before the administration of any fluids. When the catheter is capped again, it should be flushed with heparinized fluid again. The disconnection from the CRRT system does result in the loss of blood within the circuit, although for most patients this volume is inconsequential. Before discontinuing the CRRT, the anesthesiologist must plan for management of electrolyte problems, because the CRRT replacement fluid often contains bicarbonate or other electrolytes that may continue to be required during surgery.

For some patients, the CRRT will be continued during surgery. For most patients and with most CRRT systems, the optimal management requires discontinuation of the CRRT during transport and reinstitution when the patient arrives in the OR. Transporting a patient while continuing CRRT is a major effort. Most critically ill patients receiving CRRT are undergoing continuous venovenous hemodiafiltration and have, in addition to the CRRT module and two or more infusion pumps, several other pumps and monitors necessary for safe transportation. In addition to the large amount of equipment that needs to be transported, the anesthesiologist must consider whether the CRRT module has a battery backup or, alternatively, a hand crank that can be used during transportation.

When CRRT is to be instituted in the OR, a new system must be primed and available for use. In addition to the obvious inclusion of a new device to the OR environment, CRRT provides additional challenges for the anesthesiologist (Table 3).

Whenever CRRT is used during surgery, the anesthesiologist must pay even closer attention to total fluid administration, both in terms of quantity and specific replacement fluids. The therapeutic plan for CRRT that might have been appropriate for ICU management may no longer be appropriate in the OR. Two clinical examples demonstrate the importance of understanding the electrolyte composition of the CRRT replacement fluid. First, because the replacement fluid includes a buffer that requires hepatic metabolism to bicarbonate (e.g., citrate, acetate, or lactate), any intraoperative compromise in hepatic blood flow or function might cause a paradoxical acidemia. Therefore, for any procedure in which it is anticipated that liver function will be compromised, a bicarbonate-based buffer is preferred (15). Second, the composition of the replacement fluid may have to be changed when a patient has been receiving a buffered replacement fluid to correct a metabolic acidosis caused by ischemic bowel while being cared for in the ICU. Once the source for the large acid load is removed, as might occur during surgery, the electrolyte composition of the replacement fluid must be changed. Careful monitoring of arterial blood gases and electrolytes is essential to ensure normal acid-base balance.

CRRT can also be a very effective method to manage overall fluid requirements during surgery. It has been used to optimize intravascular volume while minimizing extravascular fluid accumulation. In our experience, patients who receive CRRT during surgery are less edematous and have smaller fluid shifts after major surgical procedures than do patients who have conventional fluid management during major surgical procedures.

Intraoperative management of CRRT is also facilitated by vascular access that is easily accessible to the anesthesiologist. Internal jugular vein catheters are easier to troubleshoot during a busy operation than are femoral vein catheters. In addition, the location of the dialysis catheter is an issue when the surgical procedure involves the cross-clamping of major veins. Although we have successfully continued hemofiltration in patients with femoral vein catheters after inferior vena cava cross-clamp, CRRT is greatly simplified by using a catheter located above the diaphragm.

To ensure that the CRRT is functioning properly, the anesthesiologist must monitor the access site close-ly. Kinking or other malpositioning of the catheter will compromise flows and reduce the effectiveness of the therapy. Most systems have alarms to warn the clinician of excessive line pressure. When traditional dialysis systems are used for continuous therapy, low flow alarms are not available, so careful monitoring of flow is required.

Filter clotting is a common and essentially unavoidable complication of CRRT, whether in the OR or ICU. To ensure that the therapy can be provided continuously throughout the surgical procedure, we recommend having a spare filter available in the OR in case intraoperative problems with filter patency should occur.

Hypothermia is a frequently encountered side effect of CRRT (36). The cooling is the result of high flow through a large-volume extracorporeal system. The hypothermic effect of CRRT, in addition to the reduction in body temperature that frequently accompanies general anesthesia, may have deleterious effects on the coagulation system and hemodynamic stability. The reduction in temperature that occurs with CRRT may also be associated with other metabolic sequelae, such as a reduction in oxygen consumption and increases in arterial and venous oxygen content (37). Newer CRRT systems contain in-line blood warmers that may significantly reduce the incidence of hypothermia.

The anesthesiologist must also be cognizant of the effect of CRRT on intraoperative IV drug dosing. Although many drugs can be safely titrated to clinical effect, there are a number of pharmacokinetic and pharmacodynamic characteristics that can affect drug dosing for patients undergoing CRRT (Tables 4 and 5). The first consideration is the extent to which the drug is eliminated by the kidney. Drugs eliminated primarily by nonrenal pathways are unlikely to be removed during CRRT and will not require adjustment of drug dosing (38). The continuous dosing of fentanyl, for example, which undergoes <10% renal elimination, is not altered by the presence of CRRT (39). Other drug characteristics that affect clearance by CRRT include protein binding and volume of distribution and, to a lesser extent, molecular weight, drug charge, water or lipid solubility, and membrane binding (40,41). The specific components and characteristics of the CRRT system also have an effect on drug administration. The greater the permeability of the filter, the greater the drug clearance. Similarly, the greater the surface area of the filter, the greater the drug clearance by both membrane adsorption and filtration (11).

CRRT During CPB
SCUF, ultrafiltration, and hemofiltration are forms of CRRT that have found widespread clinical application for patients who undergo surgical procedures using CPB. CPB is associated with significant extravascular fluid accumulation thought to be secondary to the hemodilution caused by the addition of the CPB pump priming fluid to the patient’s circulating blood volume. The movement of fluid from the intravascular to the extravascular space is enhanced by a dilutional decrease in intravascular oncotic pressure as well as a post-CPB inflammatory response that results in a severe capillary leak syndrome (43). The systemic inflammatory response that occurs during CPB results in the release of several inflammatory mediators, including IL-6, IL-8, C3a, C5a, and TNF-. The inflammatory response and hemodilution resulting from CPB are clinically most severe in the pediatric population. Their smaller circulating blood volumes and a disproportionally large priming volume of the CPB circuit result in a more significant hemodilution of red cells and clotting factors, as well as a more profound accumulation of extravascular fluid. The accumulation of extravascular fluid is thought to play a critical role in post-CPB pulmonary and cardiac morbidity, which often results in prolonged ventilator and ICU days.

The use of CRRT in the management of both adults and children might facilitate postoperative recovery. Journois et al. (44) studied the effects of hemofiltration during the rewarming phase of CPB in a prospective, randomized study of 32 children undergoing surgical correction of tetralogy of Fallot. Their study was designed in an effort to delineate the effects of hemofiltration on circulating levels of inflammatory mediators and measures of pulmonary and cardiac function. By removing excess intravascular fluid and low-molecular solutes such as inflammatory mediators, they hoped to attenuate the post-CPB inflammatory process and decrease the accumulation of extravascular fluid. Their results showed that patients who underwent hemofiltration had smaller plasma concentrations of C3a, C5a, IL-6, and TNF-. Moreover, the hemofiltration group demonstrated improved postoperative oxygenation, faster time to extubation, significantly decreased postoperative blood loss, increased clotting factor concentrations, and a greater post-CPB mean arterial pressure. It is interesting to note that there was no significant increase in post-CPB hematocrit in the patients undergoing hemofiltration. The ability to hemoconcentrate by using hemofiltration during CPB is limited by the inclusion of the CPB circuit within the hemofiltration circuit.

An alternative to the conventional form of hemofiltration described previously is the modified technique of ultrafiltration described by Naik et al. (45). During modified ultrafiltration, hemofiltration is performed at the conclusion of CPB by using the indwelling arterial and venous cannulae with a superimposed hemofilter. Because both the patient and CPB circuit contents undergo hemofiltration, a greater degree of hemoconcentration can occur. With use of this modified technique, authors have described decreased total body water, decreased blood loss, improved hemodynamics, and decreases in circulating inflammatory mediators.

Although the use of hemofiltration during adult cardiac surgery is not as well described, a recent article by Kiziltepe et al. (46) reported improved hemodynamics, decreased blood loss, and improved arterial oxygenation in a group of high-risk cardiac surgery patients who underwent both conventional and modified hemofiltration.

Regardless of whether one chooses the conventional or modified technique of hemofiltration for patients undergoing cardiac surgery and CPB, the benefits of hemofiltration in the pediatric patient are well documented. Whether the benefits arise from the reduction of extravascular fluid or the reduction of inflammatory mediators has yet to be determined. The potential benefit of CRRT in the management of some of the sicker adult patients who undergo surgical procedures with CPB also warrants further evaluation.

Postoperative Use
When CRRT is used in the postoperative period, the clinicians managing the therapy must be cognizant of the dynamic nature of the clinical situation. The flows and replacement fluid composition must be carefully titrated to account for intraoperative fluid shifts or blood loss and changes in intravascular volume. The patient must be closely monitored for evidence of postoperative coagulopathy or electrolyte abnormalities.

CRRT may also be introduced in the postoperative period when renal failure develops, particularly in the hemodynamically unstable patient, or when the clinical situation indicates the need for improved fluid or electrolyte management. Although there are not many objective data supporting the use of CRRT to facilitate postoperative care, Coraim et al. (47) described the use of CAVHDF for patients who underwent cardiac surgery and subsequently developed respiratory failure. The patients treated with CAVHDF had improved hemodynamic and respiratory function. Because it is likely that the postoperative patient similarly benefits from the metabolic, hemodynamic, and respiratory improvements routinely achieved with CRRT in other critically ill patient populations, the findings by Coraim et al. will probably be reproduced in other perioperative patient populations.

	Conclusion

Top Introduction Conclusion References

 
CRRT encompasses a broad array of technologies designed to address the shortcomings of CIHD and PD for the treatment of intravascular volume overload and ARF. Currently, CRRT is often used for the critically ill, hemodynamically unstable patient with renal dysfunction, fluid and electrolyte abnormalities, or both. The successful use of CRRT in this population has led to a number of continuing investigations in search of other areas in which CRRT may be of potential benefit. ARDS, sepsis, and multiple organ dysfunction syndrome are just a few of the diseases in which the advantages CRRT are being actively explored. As the use of CRRT becomes more com-monplace, it is inevitable that anesthesiologists will increasingly encounter this useful and exciting technology.

	Footnotes

 
The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the United States Government.

	References

Top Introduction Conclusion References

 

1. Kelly KJ, Molitoris BA. Acute renal failure in the new millennium: time to consider combination therapy. Semin Nephrol 2000; 20: 4–19.[Web of Science][Medline]
2. Higgins TL, Estafanous FG, Loop FD, et al. Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients: a clinical severity score. JAMA 1992; 267: 2344–8.[Abstract/Free Full Text]
3. Alkhunaizi AM, Schrier RW. Management of acute renal failure: new perspectives. Am J Kidney Dis 1996; 28: 315–28.[Web of Science][Medline]
4. Zuchelli P, Santoro A. Dialysis-induced hypotension: a fresh look at pathophysiology. Blood Purif 1993; 11: 85–98.[Web of Science][Medline]
5. Pastan S, Bailey J. Dialysis therapy. N Engl J Med 1998; 338: 1428–37.[Free Full Text]
6. van Bommel EFH, Leunissen KML, Weimar W. Continuous renal replacement therapy for critically ill patients: an update. J Intensive Care Med 1994; 9: 265–80.
7. Kelleher SP, Robinette JB, Conger JD. Sympathetic nervous system in the loss of autoregulation in acute renal failure. Am J Physiol 1984; 246: F379–86.
8. Myers BD, Moran SM. Hemodynamically mediated acute renal failure. N Engl J Med 1986; 314: 97–105.[Web of Science][Medline]
9. Valk TW, Swart RD, Hsu CH. Peritoneal dialysis in acute renal failure: analysis of outcome and complications. Dial Transplant 1980; 9: 48–54.
10. van Bommel EFH, Bouvy ND, So KL, et al. Acute dialytic support for the critically ill: intermittent hemodialysis versus continuous arteriovenous hemodiafiltration. Am J Nephrol 1995; 15: 192–200.[Web of Science][Medline]
11. Bellomo R, Farmer M, Parkin G, et al. Severe acute renal failure: a comparison of acute continuous hemodiafiltration and conventional dialytic therapy. Nephron 1995; 71: 59–64.[Medline]
12. Lauer A, Alvis R, Avram M. Hemodynamic consequences of continuous arteriovenous hemofiltration. Am J Kidney Dis 1988; 12: 110–5.[Web of Science][Medline]
13. Bellomo R, Mehta R. Acute renal replacement in the intensive care unit: now and tomorrow. New Horiz 1995; 3: 760–7.[Medline]
14. Colton CK, Henderson LW, Ford CA, Lysaght MJ. Kinetics of hemodiafiltration. I. In vitro transport characteristics of a hollow-fiber blood ultrafilter. J Lab Clin Med 1975; 85: 355–71.[Web of Science][Medline]
15. Druml W. Metabolic aspects of continuous renal replacement therapies. Kidney Int 1999; 56: S56–61.[Web of Science]
16. Bellomo R, Ronco C, Mehta R. Nomenclature for continuous renal replacement therapies. Am J Kidney Dis 1996; 28: S2–7.[Web of Science]
17. Davenport A, Will E, Davidson A. Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure. Crit Care Med 1993; 21: 328–38.[Web of Science][Medline]
18. Silverstein ME, Ford CA, Lysaght MJ, Henderson LW. Treatment of severe fluid overload by ultrafiltration. N Engl J Med 1974; 291: 747–51.
19. Lauer A, Alvis R, Avram M. Hemodynamic consequences of continuous arteriovenous hemofiltration. Am J Kidney Dis 1988; 12: 110–5.
20. Bartlett RH, Mault JR, Dechert RRT, et al. Continuous arteriovenous hemofiltration: improved survival in surgical acute renal failure? Surgery 1986; 100: 400–8.[Web of Science][Medline]
21. Silvester W. Outcome studies of continuous renal replacement therapy in the intensive care unit. Kidney Int 1998; 53: S138–41.
22. Rimondini A, Cipolla CM, Della Bella P, et al. Hemofiltration as short-term treatment for refractory congestive heart failure. Am J Med 1987; 83: 43–8.
23. Davenport A. The management of renal failure in patients at risk for cerebral edema/hypoxia. New Horiz 1995; 3: 717–24.[Medline]
24. Ossenkoppele GJ, van der Meulen J, Bronsveld W, Thijs LG. Continuous arteriovenous hemofiltration as an adjunctive therapy for septic shock. Crit Care Med 1985; 13: 102–4.[Web of Science][Medline]
25. Gotloib L, Barzilay E, Shustak A, Lev A. Sequential hemofiltration in nonoliguric high capillary permeability pulmonary edema of severe sepsis: preliminary report. Crit Care Med 1984; 12: 997–1000.[Medline]
26. Garzia F, Todor R, Scalea T. Continuous arteriovenous hemofiltration countercurrent dialysis (CAVH-D) in acute respiratory failure (ARDS). J Trauma 1991; 31: 1277–85.[Medline]
27. Gotloib L, Barzilay E, Shustak A, Lev A. Hemofiltration in severe septic adult respiratory distress syndrome associated with varicella. Intensive Care Med 1985; 11: 319–22.[Medline]
28. Gotloib L, Barzilay E, Shustak A, Lev A. Hemofiltration in severe high microvascular permeability pulmonary edema secondary to rickettsial spotted fever. Resuscitation 1985; 13: 25–31.[Medline]
29. Grootendorst AF, van Bommel EFH, van der Hovern B, et al. High-volume hemofiltration improves hemodynamics of endotoxin-induced shock in the pig. J Crit Care 1992; 7: 67–75.
30. Lee PA, Matson JR, Pryor RW, Hinshaw LB. Continuous arteriovenous hemofiltration therapy for Staphylococcus aureus-induced septicemia in immature swine. Crit Care Med 1993; 21: 914–24.[Medline]
31. Gomez A, Wang R, Unruh H, et al. Hemofiltration reverses left ventricular dysfunction during sepsis in dogs. Anesthesiology 1990; 73: 671–85.[Web of Science][Medline]
32. Honore PM, Jamez J, Wauthier M, et al. Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock. Crit Care Med 2000; 28: 3581–7.[Web of Science][Medline]
33. Ronco C, Bellomo R, Homel P. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000; 356: 26–30.[Web of Science][Medline]
34. Palsson R, Niles JL. Regional citrate anticoagulation in continuous venovenous hemofiltration in critically ill patients with a high risk of bleeding. Kidney Int 1999; 55: 1991–7.[Web of Science][Medline]
35. Tan HK, Baldwin I, Bellomo R. Continuous veno-venous hemofiltration without anticoagulation in high-risk patients. Intensive Care Med 2000; 26: 1652–7.[Web of Science][Medline]
36. Yagi N, Leblanc M, Sakai K, et al. Cooling effect of continuous renal replacement therapy in critically ill patients. Am J Kidney Dis 1998; 32: 1023–30.[Web of Science][Medline]
37. Matamis D, Tsagourias M, Koletsos K, et al. Influence of continuous haemofiltration-related hypothermia on haemodynamic variables and gas exchange in septic patients. Intensive Care Med 1994; 20: 431–6.[Web of Science][Medline]
38. Keller E. Pharmacokinetics during continuous renal replacement therapy. Int J Artif Organs 1996; 19: 113–7.[Medline]
39. Kroh UF. Drug administration in critically ill patients with acute renal failure. New Horiz 1995; 3: 748–59.[Medline]
40. Golper TA, Marx MA. Drug dosing adjustments during continuous renal replacement therapies. Kidney Int 1998; 53: S165–8.
41. Golper TA, Wedel SK, Kaplan AA, et al. Drug removal during CAVH: theory and clinical observations. Int J Artif Organs 1985; 8: 307–12.[Web of Science][Medline]
42. Tobias MT, Jobes CS, Aukburg SJ. Hemofiltration in parallel to the venovenous bypass circuit for oliguric hypervolemia during liver transplantation. Anesthesiology 1999; 90: 909–11.[Medline]
43. Miller BE, Levy JH. The inflammatory response to cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1997; 11: 355–66.[Web of Science][Medline]
44. Journois D, Pouard P, Greeley WJ, et al. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Anesthesiology 1994; 81: 1181–9.[Web of Science][Medline]
45. Naik SK, Knight A, Elliott M. A prospective randomized study of a modified technique of ultrafiltration during pediatric open heart surgery. Circulation 1991; 84: 422–31.[Web of Science]
46. Kiziltepe U, Uysale A, Corapcioglu T, et al. Effects of combined conventional and modified ultrafiltration in adult patients. Ann Thorac Surg 2001; 71: 684–93.[Abstract/Free Full Text]
47. Coraim FG, Coraim HP, Ebermann R, Stellwaf FM. Acute respiratory failure after cardiac surgery: clinical experience with the application of continuous arteriovenous hemofiltration. Crit Care Med 1986; 14: 714–8.[Web of Science][Medline]

This article has been cited by other articles:

				P. Ziemann-Gimmel, B. Pygon, F. Hurley, R. F. Albrecht, and D. E. Schwartz Treatment of Life-Threatening Hyperkalemia Using Hemoconcentration in Parallel to Venovenous Bypass During Orthotopic Liver Transplantation Anesth. Analg., March 1, 2003; 96(3): 680 - 682. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Petroni, K. C. Articles by Cohen, N. H. Search for Related Content PubMed PubMed Citation Articles by Petroni, K. C. Articles by Cohen, N. H.