CRRT: Where Are We Now?

acute kidney injury (AKI) often presents formidable risks to patients in critical care units, particularly those with associated multiorgan failure. Such patients are very likely to die in spite of the best efforts of providers. With this in mind, aggressive management of AKI using hemofiltration and/or dialytic therapy has evolved. Systems appropriate for use in pediatric patients are limited today.

History

Since the serendipitous introduction of continuous arteriovenous hemofiltration (CAVH) as described in 1977, continuous renal replacement therapies (CRRT) have developed steadily, with increasing degrees of complexity. Initial therapies driven by differential arterial and venous pressures have been supplanted by venovenous systems incorporating mechanical pumping of blood through the extracorporeal circuit. Fluid removal control has evolved from makeshift reactionary protocols (e.g., replacing removed fluid retrospectively as a percentage of that removed in the previous hour) to “real time” volumetric and/or gravimetric controlled ultrafiltration. With this complexity have come difficulties related to maintaining patient safety, but this has largely been successful.

AKI is a common problem occurring in ICU patients. Many patients afflicted with AKI in recent times also have multiple organ dysfunction (MOD). Particularly in patients with hemodynamic instability, CRRT has become a preferred method for treating AKI particularly with associated oliguria and volume overload. It has been estimated that some 5 percent of adult patients in ICUs have significant AKI during their stay.

Technology

Capabilities of machines available to perform CRRT in the United States are varied. Most depend at least to some degree on convective clearances, but most also add diffusive measures to increase solute removal. Some machines also provide for therapeutic plasma exchange. Ultrafiltration is usually monitored by one or more scales, though volumetric internal ultrafiltration methods are also available. A general outline of machine capabilities is presented in Table 1.

Table 1
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Improvements in control and accuracy of fluid removal have been particularly beneficial to small adult patients, hemodynamically unstable patients, and children.

Extracorporeal circuit

Unsubstituted cellulose membranes are not used for CRRT. Rather, more biocompatible synthetic membranes or substituted cellulose membranes are used. Because of the popularity of convective clearance in CRRT and desires to remove “middle molecules” (and potentially cytokines), membranes with high ultrafiltration coefficients (high flux) are used in hemofilters and hemodialyzers. Some systems have limited flexibility in terms of circuit size (volume) and membrane, while others are as flexible as chronic hemodialysis systems. A few systems can be used for chronic dialysis treatments, acute hemodialysis treatments, and CRRT. Of note, with increasing intensity of solute removal on a continuous basis, close attention must be paid to removal of important molecules including antimicrobials and vasopressor agents. There may be a risk of undertreatment if “usual” dialysis dosing recommendations are used. We routinely measure drug levels when available, or calculate/estimate relative urea or creatinine clearances on therapy to guide drug dosing

Vascular access

Appropriate vascular access is essential to the successful implementation of CRRT. Generally, double lumen hemodialysis catheters are used. Pediatric patients, particularly infants, present unique challenges. Access must be large enough to permit appropriate blood flows but not be so large as to promote vessel damage, obstruction to venous drainage, or remarkable safety issues during catheter placement.

Shortened CRRT circuit lives (limiting effective treatment of AKI) often are associated with inadequate vascular access. Table 2 provides examples of intravascular catheter sizes and placements for patients of various sizes.

Table 2
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Anticoagulation

Limiting thrombosis within the extracorporeal circuit is essential to proper functioning of CRRT. The mainstay of anticoagulating CRRT circuits has been unfractionated heparin. Alternatives include regional citrate anticoagulation, and saline flushes of the circuit without additional anticoagulation. The latter of these methods may be associated with more frequent clotting of the extracorporeal circuit.

Other choices may include low molecular weight heparin (difficult to safely dose in renal failure), heparinoids, thrombin antagonists, and platelet inhibiting factors. Of the available choices, regional citrate anticoagulation appears to be at least as effective as the heparin standard with demonstrated decreased risk of bleeding since there is no systemic anticoagulation effect. However, there is a risk of clinically important hypocalcemia and of citrate toxicity. These potential complications have largely been overcome by standardized protocols and appropriate adjustments for patients with impaired metabolism of citrate (e.g., liver failure).

Our practice has been to use regional citrate anticoagulation with ACD-A, calcium free dialysate, and calcium infusion to avoid hypocalcemia. Diffusive and convective clearance of citrate has generally been effective at limiting the risk of toxicity. Reports of prolonged hemofilter or dialyzer patency with citrate anticoagulation have not been consistent, though many observe perceived prolongation of circuit life with citrate.

Temperature control

Most modern CRRT systems provide appropriate warming of either blood or dialysate and replacement fluid. This is particularly important in very small patients who would otherwise lose a tremendous amount of body heat radiated from the extracorporeal circuit.

Fluid removal

Control of fluid removal on today’s CRRT systems is accurate. Either gravimetric (scales) or volumetric methods are used, most with external collection containers to weigh removed fluid. Still, operator competence at understanding the various machines is critical to patient safety. As expected, this is potentially of greater importance in small children (where there is little room for error) or hemodynamically unstable patients.

Fluids

With aggressive continuous therapies, particular attention needs to be paid to dialysate and/or replacement fluid composition. Commonly, serum phosphorus and magnesium levels drop to clinically dangerous low levels. Because of this, both may need to be supplemented in the fluids. Various protocols for this are available. Generally, fluids used should be as physiologic as possible to avoid significant imbalances.

We typically use dialysate concentrates (continous hemodialysis) with sodium phosphate added to the bicarbonate concentrate and magnesium added to the acid concentrate. Previous use of totally custom-made fluids is no longer advised because of the real risk of life-threatening errors, since standardized commercially produced fluids are now available.

Outcomes

No controlled studies have demonstrated clearly improved outcomes comparing CRRT with intermittent dialysis treatments; however, there are no studies clearly demonstrating worse outcomes with continuous therapies. Most comparisons are between CRRT and aggressive daily intermittent hemodialysis.

“Dose” of delivered therapy has been shown to be associated positively with improved outcome, but this has not been consistently demonstrated in relatively large prospective studies. Several studies in both adults and children have suggested that “early” institution of CRRT as related to degree of volume overload is associated with improved survival.

Cost

Costs of CRRT vary widely among centers. On average, CRRT appears to be more expensive than intermittent hemodialysis as currently practiced at most centers. The most costly features appear to be the increased nursing staff needed to care for patients on CRRT and the cost of replacement fluids and dialysate. Choice of treatment (CRRT versus intermittent hemodialysis) has not been consistently associated with ICU stay or subsequent chronic renal failure, quality of life, or functional rehabilitation of treated patients. Such issues clearly contribute to the overall cost or value of therapy.

CRRT is and will likely remain an important modality for treatment of AKI in the ICU in spite of lack of evidence of superior outcomes over intermittent hemodialysis. The ideal dose of therapy has not been consistently identified. It is unclear if even higher doses would have beneficial effects or if additional complications might result.

Continuous therapies are most likely to be beneficial to unstable patients with MOD who may tolerate intermittent hemodialysis poorly. Fluid management is likely to be optimized with CRRT as well. Cost is an issue, but continuous therapies using commonly available materials (e.g., use of hemodialysis machines that mix dialysate on line) are likely to decrease relative expense. Staffing in our pediatric ICU is already “one on one,” and CRRT does not typically add to this cost. There is no objective evidence that convective clearance is better than diffusive clearances in spite of the popularity of hemofiltration.

Of importance to optimal patient care is cooperation between the intensivist and renal specialist. Each has unique experiences and skills. It is unlikely that perseverating over outcomes differences between intermittent and continuous therapies will be productive. Centers should use the techniques that suit them and their patients best. CRRT is another valuable tool in the belt of physicians caring for critically ill adults and children.

Notes

[1] Joseph Sherbotie, MD, is with pediatric nephrology and hypertension division in the department of pediatrics at the University of Utah School of Medicine Primary Children’s Medical Center in Salt Lake City.

References

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