Dose prescription in CRRT - S. Goldstein

Review of CRT Modalities and Dosing

In this section, the speaker reviews the different modalities of continuous renal replacement therapy (CRT) and discusses the rationale behind dosing for acute kidney injury.

CRT Modalities

• CRT represents a continuum of therapies from slow continuous ultrafiltration to hybrid therapy.

• The three modalities that use some form of clearance have similar small solute removal rates but differ in their mechanism of clearance.

• Treatment times are all continuous, and blood flow rates need to be matched to the patient's hemodynamic status and body size.

• Slow continuous ultrafiltration removes fluid plasma water, while adding replacement fluid generates convective clearance.

• Continuous veno-venous hemofiltration uses replacement fluid plus patient net ultra filtrate in dialysate with counter-current dialysis fluid.

• Convective clearance is more efficient for larger molecules than diffusive mode.

Rationale Behind Dosing

• Dose adequacy was taken from intermittent hemodialysis to understand what is the minimum amount of dose needed for clearance to prevent negative outcomes.

• Optimal therapy is a dose above which we don't see any improvement in positive benefit.

• Renal replacement therapy can be used to treat life-threatening complications of acute kidney injury that are unresponsive to other interventions.

Practical Considerations Related to Prescription and Dose Delivery

In this section, the speaker discusses practical considerations related to prescription and dose delivery for CRT.

Prescription Considerations

• The prescription should be individualized based on the patient's clinical status and response to therapy.

• The dose should be adjusted based on the patient's hemodynamic stability, fluid balance, and electrolyte status.

• Anticoagulation is necessary to prevent clotting in the circuit but can increase bleeding risk.

Dose Delivery Considerations

• Dose delivery can be affected by factors such as catheter placement, blood flow rate, and filter type.

• Monitoring of effluent volume and laboratory values is essential to ensure adequate dosing.

• Complications such as hypotension, electrolyte imbalances, and infection can occur with CRT.

Continuous Renal Replacement Therapy Dose Requirements

This section discusses the dose requirements of continuous renal replacement therapy (CRRT) and how it compares to intermittent hemodialysis.

CRRT vs. Intermittent Hemodialysis

• As more therapies are done during the week, the standard kt/v will increase.

• CRT over a week has the potential to provide significantly more clearance than intermittent hemodialysis.

• A greater standardized kt/v can be achieved with CRT compared to IHD.

• Even daily intermittent hemodialysis may not afford the same clearance over a week that CRT does.

• Standard care for patients on maintenance dialysis provides less clearance than CRT.

Calculating CRT Dose

• The delivered dose is considered equivalent to the total fluid volume expressed as a weight-adjusted hourly fluent rate.

• For CVVH, the affluent rate is the rate of replacement fluid in mils per hour plus net ultrafiltrate in mils per hour.

• For CVVHDF, the fluent rate is calculated by combining replacement fluid rate, dialysis fluid rate, and net ultrafiltrate.

• The average 70-kilo patient leads to a dose of dialysis of 30.1 ml/kg/hour.

Additional Aspects of CRT Dose

• In chronic or intermittent hemodialysis, blood flow rate generally determines clearance. In CRT, the blood flow rate is significantly higher than the affluent rate and therefore there is near saturation.

• Dosing medications for a particular patient at 35 ml/min (moderate CKD) should be considered.

Minimum Delivered Dose

• The KDIGO recommendation states that a delivered affluent volume of 20 to 25 ml/kg/hour should be prescribed or delivered in patients who have acute kidney injury.

• A higher dose should be prescribed in order to deliver this 20 to 25 ml/kg/hour due to downtime changing of bags access issues etc.

Famous CRT Dose Trials

• Dr. Ronco's study was a single-center randomized control trial evaluating the dose effect of CRT on outcome and introduced the concept of CRT dose in a randomized way.

• The NIH VA ATN trial spearheaded by Dr. Paul Epskey and the RENAL trial spearheaded by Reynaldo Bellomo provide insight into what the minimum dose should be.

Intensive Therapy vs Less Intensive Therapy

This section discusses the results of two studies that compared intensive renal replacement therapy (RRT) to less intensive RRT.

Comparison of Different Doses of RRT

• Patients who received higher doses of 45 or 35 mils per kilo per hour demonstrated improved survival compared to patients who received 20 mils per kilo per hour.

• The VA NIH a TN study looked at intensive therapy versus less intensive therapy and found no significant difference in patient outcome for patients who received the less intensive versus the intensive strategy.

• The Renal Study looked at CVVHDF out of New Zealand and Australia, comparing higher intensity lower intensity CRT. There was no difference with respect to mortality and RT intensity so patients who received the higher intensity CRT did not have better survival.

Recommended Dose Intensity

• KDOQI recommends delivering the fluent volume of 20 to 25 mils per kilo or per hour based on evidence from these two studies.

Overall, there is no significant difference in patient outcomes between intensive and less-intensive RRT strategies.

Aspects of Medical Management Beyond Small Solutes

The section discusses the considerations beyond small solute or urea clearance when prescribing renal replacement therapy.

Other Considerations in Prescribing Renal Replacement Therapy

• Positive fluid balance may be an independent risk factor for mortality in Aki patients. Control of fluid balance is important.

• Besides small solutes, other things are removed by CRT membranes. Phosphate control is important since relatively high doses of CRT can cause hypophosphatemia. Drugs that are not highly protein-bound and nutrients should also be considered.

• Fluid balance is a key factor affected by CRT. Drug dosing and acute kidney injury have received attention recently, especially in those receiving renal replacement therapy.

• Different CRT-specific factors can affect drug removal, including filter composition and dialysis dose. Antibiotics, anticoagulants, and other medications require special consideration when dosing for patients receiving continuous renal replacement therapy.

Conclusion

• Consistent data from the ATN and RENAL trials show no benefit of increasing doses above 20 to 25 mils per kilo per hour. Delivered doses in AKI may often be lower than prescribed doses, so it's important to measure this to achieve an adequate delivered dose.

• Prescribing a range of 25 to 30 mils per kilo per hour can minimize interruptions in CRT but should be individualized to meet each patient's needs taking into account factors other than small solute clearance. Urea clearance is not the only thing we should pay attention to but it is the first thing we should consider.