Continuous Renal Replacement Therapy

Kelly Monaghan, DVMSmall Animal Internal Medicine

August 28, 2009

Indications

• Toxins/drugs• Leptosporosis • Oliguric/anuric renal failure• Acute kidney injury that is not responsive to

traditional management• Acute kidney injury in critically ill patients• SIRS, sepsis?

Benefits

• More closely approximates normal kidney function

• Slower blood and dialysate flow rates– Smaller patients

• Less dramatic changes/shifts• Cage-side system• Less maintenance required for

machine

Basic Principles

• Blood is diverted from the patient to the unit• Anticoagulants are added to the blood before

the filter• Uremic toxins are removed and electrolytes

normalized• Blood is returned to the patient

Diffusion

• BUN and creatinine diffuse freely into dialysate through semipermeable membrane

• Limited by the size of the membrane pores

• Substances in dialysate also diffuse into blood

Convection• Blood traveling within

semipermeable membrane is exposed to a positive transmembrane pressure

• Pressure pushes fluid out of the blood (with toxins and electrolytes) and across the semipermeable membrane

• Ultrafiltrate is removed from the dialyzer and disposed of as effluent

• Larger molecules are more effectively cleared by this process than by diffusion

Adsorption

• Molecules adhere to the dialysis membrane and are removed from circulation

• May be of benefit for SIRS/sepsis– Potentially requires more frequent filter changes

MembraneMembrane

The Machine

• Dialyzer• Four pumps– Blood pump– Dialysis solution pump– Replacement solution pump– Effluent pump

• Solutions are continuously weighed by machine

Modes of Operation

• SCUF• CVVH• CVVHD• CVVHDF

Filtration = ConvectionDialysis = Diffusion

SCUF

• Slow Continuous UltraFiltration• Least complex and most rapid (few hours)• Purely convection• Ultrafiltrate is not replaced in this modality• Congestive heart failure, fluid overload

SCUF

CVVH

• Continuous Veno-Venous Hemofiltration• Similar to SCUF (convection) but removed

fluids are replaced with sterile, balanced electrolyte replacement solution to prevent hemoconcentration

• Effective at removing uremic toxins through convection only

CVVH

CVVHD

• Continuous Veno-Venous HemoDialysis• Primarily diffusive therapy • Similar to intermittent hemodialysis• Toxins diffuse across membrane into dialysate• Beneficial substances diffuse into blood from

dialysate

CVVHD

CVVHDF• Continuous Veno-Venous HemoDiaFiltration• Primary modality for our patients• = CVVH (convection) + CVVHD (diffusion)• Diffusion guides movement of uremic toxins

and electrolytes• Convection causes movement of fluid and

molecules out of blood

CVVHDF

Complications

• Clotting of dialyzer/circuit (blood loss)• Hemorrhage• Thromboembolic events• Sepsis• Dialysis dysequilibrium (not reported in CRRT)

Anti-coagulation

HEPARIN

• Requires systemic anti-coaulation

• Less intensive monitoring required

• Reported shorter filter life (Kutsogiannis et al. Kidney Intl. 2005)

• Heparin-induced thrombocytopenia (people)

CITRATE

• Decreased risk of hemorrhage

• Requires calcium supplementation

• Risk of iatrogenic hyper/hypocalcemia

• Risk of metabolic alkalosis as it is metabolized

• More intensive monitoring

Veterinary Literature• Only one paper by Diehl et al. JVECC 2008– Retrospective on 17 dogs and 16 cats that received

CVVHDF– Regional citrate anticoagulation was performed– Median duration of CRRT in dogs was 16.3 hours and

in cats was 11.5 hours (until values normalized)– UOP was not consistently monitored and therefore

not reported– Complications: hypokalemia, CNS signs,

hyper/hypocalcemia, hypothermia, alkalosis, filter clotting, chronic kidney disease

– 41% of dogs and 44% of cats survived to discharge

Intermittent HD versus CRRT

Which is the better choice for

our patients?

Evidence-Based Medicine

• No veterinary studies in this area• Several human papers that try to compare • To date, there is no clear answer

Theory of Practice

Intermittent HD CRRT

Literature• Ricci and Ronco. Crit Care Med 2008

– Review article– 80% of centers use CRRT, 17% use IHD– Studies comparing the modalities have found conflicting results– Surviving Sepsis Campaign concluded that they should be considered

equivalent in AKI– Problem in all of the studies is that despite attempts at randomization, CRRT

population has significantly greater severity of illness scores and despite improved fluid balance and azotemia control, still had higher mortality in some studies

– Metaanalysis by Kellum et al in 2002 found that after stratifying 1400 patients according to disease severity, CRRT was associated with a significant decrease in the risk of death when similar patients were compared

– Metaanalysis by Tonelli et al in 2002 found no difference between the techniques

– Concluded that the most important point with either is achieving an adequate dose

Literature

• Bell et al. Intensive Care Med 2007– Concluded that there was better renal recovery

for patients receiving CRRT than those that got IHD but no difference in mortality

– Study does not discuss dose, time on machine, or severity of illness for each population

– Metha et al 2001 had similar results

Literature

• Lins et al. Nephrol Dial Transplant (2009)– Randomized controlled trial stratified for disease

severity– No difference between IHD and CRRT was

observed in duration of ICU stay or hospitalization– Renal recovery at the time of discharge was

comparable between groups– No difference in mortality between groups– Cross-over was allowed between groups

Literature

• Rauf et al. Intensive Care Med (2008)– Evaluated costs and outcomes associated with each

modality– Patients in CRRT group had higher severity scores, higher

incidence of sepsis and respiratory disease• Significantly longer hospitalization stays• Less likely to have chronic renal insufficiency

– RRT method did not affect the likelihood of renal recovery, in-hospital survival, or survival during 1 year follow-up

– Mean adjusted cost through hospital discharge was $93,611 for IHD patients and $140,733 for CRRT patients

How do we apply this?

• General consensus that CRRT may be better for cardiovascularly unstable patients

• Veterinary dialysis patients tend to correlate with the most critically ill and often, cardiovascularly unstable human patients

Future Directions

• IHD for toxins, transient insults• CRRT for critical patients and follow-up IHD if

needed• Consider use in septic AKI

Use in Sepsis / SIRS • Ronco et al. Artificial Organs (2003)

– Peak-concentration theory: cutting peaks of soluble mediators – CRRT non-selectively removes peak concentrations of pro- and anti-inflammatory mediators– Non-selective adsorption produced in excess may improve survival– May require higher doses of CRRT as compared with renal injury alone

• Peng et al. Burns (2005)– CVVHDF given to burn patients with sepsis– Plasma level of endotoxin, TNF-α, IL-1β, IL-6, and IL-8 significantly lower than pre-treatment

or control– Endotoxin not present in effluent– No significant differences in median hospitalization or mortality

• Joannidis M. Seminars in Dialysis (2009)– Review– Use of standard CRRT in absence of AKI did not demonstrate changes in levels of cytokines or

complement at standard doses (DeVriese et al 1999)– High adsorption hemofiltration (changing filter q3h in CVVH) showed significant reduction in

IL-8 and IL-10 as well as faster reduction in vasopressor requirements (Haase et al 2007)– High volume hemofiltration used to increase convection and adsorption utilizing filtration

rates up to 215ml/kg/h showed improved hemodynamic stability and survival

Cost

• ~$1100 per day for treatment• Estimate $10,000-15,000

•Owner should be prepared for at least 48-72 hours of treatment

For More Info or Questions

• Anyone on dialysis team• Happy to consult, talk with owners or RDVMs• Personal contact info– KellyMonaghan@gmail.com– Pager: (508) 312-8006– Cell: (225) 278-1791– Home: (508) 779-0562

QUESTIONS?