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Continuous Renal Replacement Therapy

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Presentation on theme: "Continuous Renal Replacement Therapy"— Presentation transcript:

1 Continuous Renal Replacement Therapy
Kelly Monaghan, DVM Small Animal Internal Medicine August 28, 2009

2 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? Pull papers on use w/ SIRS/Sepsis

3 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 Less dramatic and abrupt changes in renal values

4 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 Delete slide??

5 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 Movement of molecules in a solution from an area of high concentration to an area of low concentration Dialysate solutions must be sterile and balanced and free of toxins, metals, etc (can be used to correct acidosis)

6 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 Can dehydrate patient or result in electrolyte imbalances if fluids/electrolytes are not replaced

7 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 Membrane

8 The Machine Dialyzer Four pumps
Blood pump Dialysis solution pump Replacement solution pump Effluent pump Solutions are continuously weighed by machine

9 Filtration = Convection
Modes of Operation SCUF CVVH CVVHD CVVHDF Filtration = Convection Dialysis = Diffusion

10 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 No replacement solution Aims to remove fluid, not solutes


12 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 Purely convective w/ replacement solution Best for middle sized molecules

13 Pre / Post Filter Replacement
Pre-filter Replacement Replacement solution mixed with blood before passing through the filter Decreased risk of filter clotting due to hemodilution Decreased overall efficiency Post-filter Replacement Replacement solution is mixed with blood leaving the filter Higher risk of filter clotting due to relative hemoconcentration within the filter Improved efficiency Pre-filter dilution Instills replacement solution into blood b/f entering filter so dilutes out patient’s blood in the filter Decreased filter clotting Decreased efficiency Lower risk of hypotension Post-filter dilution Replacement solution mixes w/ blood after blood has passed through the filter Blood going through filter is more hemoconcentrated Increased risk of filter clotting Increased risk of hypotension since using patient for source of volume that ultrafiltrate will be drawn More efficient Not likely to be too efficient if doses are calculated beforehand LSU uses this modality and reports low incidency of clotting and hypotension


15 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 Purely diffusive Most like IHD Removes small molecules


17 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


19 Pathophysiology (Ronco and Ricci. Intensive Care Med 2008)
CRRT requires continuous contact of patient’s blood with foreign surfaces which activates the coagulation and complement cascade, leukocytes, and platelets Activated leukocytes release inflammatory mediators and induce oxidative stress, transforming lipids and proteins and contributing to endothelial injury Activated platelets aggregate and stimulate thrombin generation Bio-incompatibility of RRT materials potentially enhances coagulation and inflammation pathways that are already triggered in the critically ill patients and that RRT is used to treat

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

21 Anti-coagulation HEPARIN CITRATE Requires systemic anti-coaulation
Less intensive monitoring required Reported shorter filter life (Kutsogiannis et al. Kidney Intl. 2005) Heparin-induced thrombocytopenia (people) Decreased risk of hemorrhage Requires calcium supplementation Risk of iatrogenic hyper/hypocalcemia Risk of metabolic alkalosis as it is metabolized More intensive monitoring Human medicine debates this issue regularly and the literature seems to favor citrate due to lack of systemic anti-coagulation and prolonged circuit life However, citrate associated w/ much more intense monitoring of acid/base and calcium as well as ACT; thereby increasing cost Heparin Dosing Remember: must enter into machine as ml/hr LSU aims for ACT ~200s Start of therapy In the absence of coagulopathy (ACT >150) give 25 u/kg hep bolus Recheck ACT. If <180 repeat bolus (max of 3 total boluses) During CRRT Start heparin infusion 20u/kg/h If ACT<180, increase heparin by 1 u/kg/hr If ACT>220, decrease heparin by 1 u/kg/hr If ACT<150, bolus 15 u/kg heparin and increase CRI Monitor ACT q30min after any change Monitor ACT q1-2 hr once stable

22 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 Patients received CRRT for ARF and A on CRF over 4 years All patients failed standard medical management prior to RRT3 dogs, 2 cats died before collection of recheck labwork; all others showed improvement in the degree of azotemia 2 dogs and 1 cat developed hypotension (1 dog and the cat arrested) 10 dogs and 15 cats developed hypothermia pRBC transfusion was required in 4 dogs and 4 cats 4 cats and 5 dogs developed iatrogenic metabolic alkalosis Citrate anticoagulant: 4 dogs and 2 cats developed iatrogenic hypercalcemia 15 dogs and 13 cats developed hypocalcemia during CRRT (4 of each were clinical) CNS 1 dog developed twitching and vocalization which resolved w/ mannitol (6.1% URR over 12.5 hrs) 1 cat developed nystagmus, head tremors, and facial fasciculation which resolved with mannitol (2.6% URR over 31.5hrs) 1 cat developed hyperexcitability, twitching, and anxiety which spontaneously resolved in 48 hours (9.2% URR over 9.5hrs) 1 cat with an 8 year seizure history developed progressive obtundation, convlusions, coma and arrested (4.8% URR over 16.5 hrs) 9 filters failed due to clotting In 6 dogs and 9 failed in 7 cats; 4 dogs had concurrent catheter clotting Complications Hypokalemia in 71% of dogs and 47% oc cats due to low potassium in dialysate CNS signs in a cat with chronic hypernatremia due to rapid decrease in the sodium (not clear if this was the cause of death in this patient) Total hypercalcemia and ionized hypocalcemia due to citrate anticoagulation Metabolic alkalosis also possible b/c the citrate is metbolized to bicarb by the liver Filter clotting Significant hypothermia CNS signs May have been due to ionized hypocalcemia, cerebral infarct, cerebral vasospasmm, cerebral hypoxia, systemichypertension, intracranial hemorrhage, or dialysis disequilibrium syndrome as a result of an excessively rapid lowering of solutes from the extracellular fluid relative to the intracellular space resulting in cerebral edema Recommended URR in IHD is 25-50% DDS has never been reported in CRRT in humans! Incidence of induction of CKD was 6% in cats while no dogs developed CKD

23 Intermittent HD versus CRRT
Which is the better choice for our patients?

24 Evidence-Based Medicine
No veterinary studies in this area Several human papers that try to compare To date, there is no clear answer

25 Theory of Practice Intermittent HD CRRT
Research in humans has failed to identify a difference in outcome/mortality b/t the two modalities Felt in human medicine that CRRT is more appropriate for the cardiovascularly unstable and many comparison papers are biased in that theses patients are commonly in the CRRT group CRRT more common in human medicine but tends to be more expensive

26 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 CRRT may be better in terms of total water and solute removal over 24 hours and hemodynamic tolerance, but IHD can remove much more water and solute per hour and it does not require continuous anticoagulation or complete immobilization the question of superiority of a modality for renal support may be artificial Reasonable to transfer a patient from CRRT to IHD as their clinical status changes or vice versa

27 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

28 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 Cross-over of treatment was allowed and reasons included coagulation problems (CRRT to IHD) and hemodynamic instability (IHD to CRRT) 54% of patients were not randomized for medical reasons (hemodynamic instability or coagulation problems) or non-medical (availability of procedure, time) Seems that these patients were included in final analysis though difficult to say for sure based on how paper is written) No differences were noted in randomized or non-randomized groups Randomized patients were overall younger and had lower severity scores

29 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

30 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

31 Future Directions IHD for toxins, transient insults
CRRT for critical patients and follow-up IHD if needed Consider use in septic AKI

32 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

33 Cost ~$1100 per day for treatment Estimate $10,000-15,000
Owner should be prepared for at least hours of treatment

34 For More Info or Questions
Anyone on dialysis team Happy to consult, talk with owners or RDVMs Personal contact info Pager: (508) Cell: (225) Home: (508)


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