Renal Replacement Therapy

CCM 2020 Review - https://journals.lww.com/ccmjournal/Fulltext/2019/05000/Renal_Replacement_Therapy_in_the_ICU.12.aspx

CCM 2021 History of RRT https://journals.lww.com/ccmjournal/Fulltext/2021/03000/ICU_Based_Renal_Replacement_Therapy.2.aspx/

iHD

• Blood flow = 300-400 ml/min = why it's poorly tolerated by critically ill patients, hypotension common.
• Dialysate flow 500 ml/min (hence highly effecctive solute removal)
• done for 3-4h 3x/week
• fluid removal is limited by vascular refill, thus generally it is not possible to remove more than 2-3L in a single session even in compensated patients.

Used to be the only option in 1970s - vasopressor dependent patients unable to tolerate fluid and solute shifts.

Main current benefit is allowing better mobility in patients who can tolerate it

Peritoneal Dialysis

Better preservation of residual kidney function. Mortality benefit if used vs iHD at initiation of long term dialysis in outpatients.

However, in the ICU it does not achieve adequate solute or, especially, volume control - esp if highly catabolic or trauma. Glucose rich PD solutions also caused hyperglycemia.

CRRT

Ref: http://dx.doi.org/10.1053/j.ajkd.2016.03.427

POSSIBLY a higher likelihood of kidney recovery when compared with iHD when used in ICU (1.7x rate of dialysis dependence when iHD used in cohort studies, but no difference in RCTs which may reflect who is included - Schneider ICM 2013). Preferred in hemodynamic instability. Less effective clearance of solutes than iHD (particularly urea clearance). Generally done continuously 24/h per day. Also, should be exclusively used in patients with ICP, as iHD can induce brain water shifts.

History of CRRT

1st version: connect artery to a hemofilter then back to a vein = 9-10 ml/min of ultra filtrate, then give some back with a replacement fluid. Called Continous arteriovenous hemofiltration (CAVH)

Problem: clearance not high enough to control uremia in catabolic patients. Thus, add a dialytic component (=flow passed dialysis solution as in iHD. Generally done countercurrent) -> continuous hemodiafiltration (CAVHDF).

Next problem = requires 2 access points (artery and vein). Solution => double lumen venous catheter with a pump (to replace the a -> v pressure gradient). This also allows for active control of the ultra filtrate rate.

Later innovations: large replacement fluid bags (5L) which can either be given pre-filter or post-filter. Higher blood flow / larger filters improving performance (solute or volume clearance)

Types:

CVVH (hemofiltration), CVVHD (hemodialysis), CVVHDF (hemodiafiltration), and SCUF (slow continuous ultrafiltration)

Removes solute through:

• convection (CVVH and CVVHDF, driven by transmembrane pressure gradient)
• diffusion (CVVHD and CVVHDF, driven by solute concentration gradient)
• adsorption (into the membrane)

Qef = effluent rate= Qnet + Qsubstition

From Macedo and Mehta 2016 AJKD

SCUF works by ultrafiltration without fluid substitution (esp useful for fluid removal)

Similarly, whether the substitution fluid is introduced pre- or post- filter influences clearance of molecules.

Pre-dilution = prevents clotting and extends filter life due to less concentrated fluid. Post-dilution fluid set up leads to larger solute clearance.

Comparison of modes: https://litfl.com/ihd-vs-crrt-vs-sled/

####CVVH (continuous venovenous hemofeiltration)

• no dialysate flow

####CVVHD (continuous venovenous hemodialysis)

####CVVHDF (continous venovenous hemodiafiltration - both)

• Blood flow 100-300 ml/min (often 150-200), dialysate flow rate 100-300 (usually 150 ml/min), runs for 6-12 hours.

SLED (sustained low - efficiency dialysis) or SLEDD (sustained lw-efficiency daily dialysis)

Not exactly iHD or CRRT... 6-12 hour runs, same blood flow rate as CRRT but dialysate rate is faster -> shorter session. Often performed at night.

• no need to anticoagulate. can be done through a fistula (not so with CRRT)
• similar solute removal to CRRT, not as good as iHD

Uses

CRRT can completely separate net fluid balance and composition adjustments (meaning, can change tonicity and volume entirely independently). Fluids are generally premanufactured then adjusted if needed.

From Macedo and Mehta 2016 AJKD

It is recommended to use bicarbonate instead of lactate as a buffer in patients with AKI, circulatory shock, liver failure, or lactic acidosis (don't understand the last - possibility of lactate indicating impaired clearance of lactate?). Note: citrate is also a buffer (metabolized to bicarbonate in the liver) if this is used as an anticoagulant.

Note: IL6, 8, 1, and TNFalpha removed by convection - impairs ability to generate fever in response to infection.

Note: Studies suggest that 20-25 ml/min solute clearance is adequate - outcomes unlikely to be improved by going faster.

Toxin Removal

CRRT is more effective than iHD removing toxins with large volume of distribution, tight tissue binding, or slow intercompartmental transfer.

CRRT not effective for highly protein bound drugs, low mol weight (e.g. Lithium)

When to start:

STARRT-AKI - large RCT comparing accelerated vs standard initiation (only when urgent need). No mortality difference, but more patients stay on dialysis and there are more adverse events if you start earlier.

Net Ultrafiltration Rate (NUF) - how fast to remove fluid? Several ongoing trials

Access and Circuit Maintenance

Tunneled, cuffed, double lumen, polymeric silicone catheter are recommended for use if more than a week of therapy is needed (average duration < 2 weeks in all comers). Larger diameter = higher flow rates. KDIGO 1A indication.

Should lock with citrate (instead of heparin) due to lower risk of infection, bleeding, and thrombosis.

Fistulas / Grafts should not be used for CRRT (risk of needle dislodgement and bleeding)

RIJ > LIJ (due to lower flow rates with head movements). Femoral is next choice, unless they are obese (equal rate of dysfunction) Subclavian discouraged due to stenosis risk (same with PICCs)

Proper length (terminating in R atrium, not SVC) led to lower complications -> use 20cm in R IJ and 24cm in L IJ. At least 24cm length should be used for femoral (to avoid recirculation) -

Morgan D, Ho K, Murray C, et al: A randomized trial of catheters of different lengths to achieve right atrium versus superior vena cava placement for continuous renal replacement therapy. Am J Kidney Dis 2012; 60:272–279

Monitoring

Urea kinetics in iHD

Total effluent volume in CRRT

Too high dose => change med pharmacokinetics, remove amino acids and essential minerals. Perhaps worse renal recovery (and hypophos discussed below)

Anticoagulation

doi: 10.1093/ndtplus/sfp136

Not needed for iHD, but needed for CRRT or SLED due to lower flow rates. (Because blood touching the extracorporeal circuit promotes clotting).

1. Citrate regional anticoagulation: Citrate infusion into the arterial tubing -> chelates calcium (then the complex is removed by dialysis clearance) -> cascade inhibited. Goal is to keep clotting time over 160s. Serum ionized calcium must be monitored.

• titrated based in iCal levels.. generally to 0.9-1.0 because critically ill patients are thought to have slightly lower levels than the normal 1.0-1.25)
• tox: in liver failure (not metabolized to bicarb) = . Monitor by ratio of total Ca/iCa. Over 2.5 suggests citrate tox. Hypocalcemia (because ca is complexed to citrate) results if can't be metabolized.
• upside less bleed risk. Downside - more complicated protocols, risk of hypoca in liver failure

2. Heparin

• target aPTT generally 60-80
• risk of HIT, bleed, increased antithrombin 3 clearance -> heparin resistance.

3. Intermittent saline solution flushe every 15-30 minutes. (keeps fibrin strands from accumulating.).

4. Nothing - this works ok as long as high blood flow rate is maintained.

Should monitor filter clearances (Cef: Cp ratio). <0.8 predicts clotting.

##Complications

Hypotension

Occurs when Qnet (removal) exceeds vascular refilling rate (from intracellular and interstitial compartments).

Can lead to transient decreased perfusions (e.g. in ATN, autoregulation is impaired) that delays recovery.

Electrolytes

High dose CRRT can lead to hypophos (fast mass transfer from tissues, pore size), hypomag