CRRT IN ACUTE KIDNEY INJURY Dr Umut Selda Bayrakçı Yıldırım Beyazıt University, Ankara, Turkey Acute renal failure is not a “cute” renal failure Druml W, 2004  The epidemiologic importance of AKI as a public health problem is underscored  because renal function can easily and practically indefinitely be replaced by modern renal replacement modalities, AKI presents a rather harmless complication  Despite the advances in the ability to provide dialysis to children, the out come of AKI remains surprisingly poor  MORTALITY in critically ill patients  53 % in the ATN trial  44.7 % in the RENAL trial  Even a small reduction in the renal function (0.3 mg/dl SCr increase) is a risk factor for morbidity and mortality in hospitalized patients.  It is not a problem restricted to the kidneys  It’s a systemic disease process AKI exerts a fundamental impact  On the course of disease The evolution of associated complications Prognosis Independently from the underlying disease Patients with ARF, die not (only) with but (also) from AKI; acute renal failure is not a “cute” renal failure but a dangerous condition. Druml W, Intensive Care Med 2004, Bellomo R, et al. Lancet,2012, Hobson CE et al. Circulation 2009, Coca SG et al. Am J Kidney Dis 2009, Murugan R, Kellum JA. Nat Rev Nephrol 2011 Management of AKI  Largely supportive  Aimed preventing of life-threatening fluid or electrolyte complications  Avoiding or minimizing further renal injury  Providing appropriate nutrition to allow recovery from acute illness and renal dysfunction  Severe AKI or milder AKI in association with severe fluid overload or solute imbalance may require renal replacement therapy (RRT)  When RRT is indicated  What is the OPTIMAL RRT modality When to start?  Should clinicians wait for  Frank anuria?  Unequivocal signs of uremia?  Fluid overload?  Should treatment be indicated proactively?  Are there reliable indices helping to choose RRT timing? Absolute indications to start RRT  Uremic complications, for example encephalopathy, pericarditis, bleeding.  Serum urea at least 36 mmol/l (100 mg/dl).  K+ at least 6 mmol/l and/or ECG abnormalities.  Mg at least 4mmol/l and/or anuria/absent deep tendon reflexes.  Serum pH 7.15 or less.  Urine output less than 200 ml/12 h or anuria.  Diuretic-resistant organ edema (i.e. pulmonary edema) in the presence of AKI. Acute Dialysis Quality Initiative (ADQI) workgroup,2001 When to start?  Not only the presence of AKI but also its severity should be assessed: pediatric RIFLE (Risk, Injury, Failure, Loss, End stage)  Severe AKI and/or rapidly deteriorating kidney function (towards “F” level) RRT initiation should be considered.  Particularly if there was failure to respond to initial therapy.  Critically ill patients with mild to moderate AKI (i.e. RIFLE category R/I): the most challenging  Decision should be tailored dynamically  Sometimes we should consider RRT in earlier stages of AKI:  Severe sepsis  Reduced renal reserve  Primary diagnoses associated with high catabolic rates (septic shock, major trauma, burn, injury)  Gastrointestinal bleeding, rhabdomyolysis placing considerable demand on kidney function  A positive fluid balance and overt clinical fluid overload When RRT is indicated?  30 children  Children with volume excess of 10% or less improved survival  21 children on CRRT  Mean volume excess 16%  Mean volume excess 33% survived did not survived  116 children with AKI, CRRT, 13 different center  Mean volume excess 14% survived  Mean volume excess 25% did not survived Lane PH et al. Bone Marrow Transplant 1994, Goldstein et al Pediatrics 2001 Goldstein et al. Kidney Int 2005 When RRT is indicated?  As soon as fluid overload occurs  unless there is excessive solute load  Reasonable TRESHOLD for initiation of RRT: fluid overload of 15% *BUN levels at initiation of RRT was not associated with survival (increased in nonsurvivors) Bunchman TE.Nature Clinical Practice 2008 When to start?  1847 ICU patients with AKI requiring RRT  Relationship between biochemical, physiological and comorbid factors at time of RRT start and ICU mortality  Independent risk factors for ICU mortality  Mechanical ventilation  Oligoanuria  Serum urea  Cardiovascular failure  Failure to correct acidosis and development of more organ failure within 48 hours of RR  Survivors tended to have higher creatinine and lower urea levels at the start of RTT YH Chou et al. Crit Care 2011. Take home message-1  RRT should be recommended for AKI in critically ill patients before organ failure and and metabolic derangements have reached the slippery threshold of irreversibility!!  Creatinine is not an ideal biomarker for decision on RRT timing  New biomarkers will hopefully improve the performance of creatinine, urea and RIFLE The message-2  The decision when to start RRT should be established case by case and guided by  Associated dysfunction of other organ systems  patients’ AKI severity  Urine output  Serum pH  locally available technics and devices Stuivenberg Hospital Acute Renal Failure Project (SHARF)  RRT patients have higher mortality (43 vs 58%)  Longer ICU and hospital stay compared to patients treated with conservative approach Elseviers MM et al. Crit Care 2010 Which is the best dialysis modality The two most important factors that influence choice of dialysis:  The indication for dialysis  Overall clinical status of the patients *The decision will be based upon  Specific patient characteristics  Patients requirements/limitations  The status of major organ systems  LOCAL EXPERTISE with specific dialysis techniques  Facility experience  Local resources Should intermittent RRT or continuous RRT be used  No suitable powered randomized controlled trials  Results of present studies do not suggest a difference in patient survival  On the basis of patient survival all seem to be acceptable  State of the art  Clinical status of the patient  Intermittent HD requires careful use in patients with impaired hemodynamic status CVVH  Venovenous forms of CRRT is considered superior to other forms of CRRT because of  Lover risk of hemorrhage  Less frequent circuit clotting  More predictable driving pressure through the hemofilter Advantages of CVVH 1. Continuous solute clearance and ultrafiltration  Gradual removal provided by hemofiltration **Ideal modality for patients with cardiovascular instability and hypotension  Continuous removal  Fluid restriction is usually unnecessary  Freedom to provide large volumes of nutritional support, drugs, blood products etc.. Advantages of CVVH 2. Specific metabolic advantage  Wide variety of metabolic problems can be corrected easily  Severe metabolic acidosis  Lactic acidosis  Electrolyte abnormalities (s.a. hyperkalemia)  Superior control of uremia than intermittent HD  It can also be adopted to gradually correct hyperosmolar states 3. Less likely to lead to cerebral edema 4. Removal of mediators of inflammation Cost of dialysis equipment (in U.S. dollars) Manual Automated İntermittent Continious Modality PD PD HD HF Device Ultra Set (Y-set) Freedom cycler C3 Prisma Manufacturer Baxter Fresenius Gambro Gambro Cost per unit $6.95 $12,295.00 $18,000.00 $25,000.00 Cost of additional supplies 1.5% Dianeal $24.43/2 L Pediatric tubing set $32.00 each Peritoneal dialysate as at left 100HG dialyzer $50.00 each; pediatric bloodlines $11.40 each M60 hemofilter set (filter and bloodlines) $160.00 each Normocarb dialysate concentrate $20.00/3.0L Flynn JT, Pediatr Nephrol 2002 GUIDANCE FROM THE LITERATURE 1995: 42 children (following repair of congenital heart dis):  21 PD 21 HF; 9 CAVH, 12 CVVH Survival: identical Fluid removal, urea and creatinine clearance, and caloric intake superior in HF Fleming et al, J Thoracic Cardiovasc Surg, 1995 Adults: Because of limitations in clearance and difficulties in fluid removal PD is rarely used in ARF Pediatrics: PD used to be the first choice; technical difficulties of HD in infants and young adults 1997: Comparison of HD and hemofiltration in pediatric ARF  122 children with ARF (retrospective)  58 HD  64 HF  Survival: 83% in HD, 48% in HF group Higher percentage of children with primary renal dis in HD group Higher percentage of patients with sepsis in HF group, greater severity of illness in HF Maxvold et al; Am J Kid Dis 1997 Comparison of 3 dialysis modality  279 children with ARF and/or inborn errors of metabolism (retrospective)  59 PD  140 HF  80 HD  Overall survival was 53%  Variation in survival among modalities for certain diagnoses Comparison of 3 dialysis modality  ARF following bone  ARF following repair of marrow transplant congenital heart disease  %78 intermittent HD  100% intermittent HD  33% PD  33% PD  21% HF  50% HF  Hemodynamic instability  affect patient outcome  predictive of modality choice  patients who were the most hemodynamically unstable were usually treated with either HF or PD whereas stable patients were usually treated with intermittent HD. Bunchman TE, J Am Soc Nephrl, 1999, abstr Limitations:  Retrospective  Single center study designs  Small patient numbers  Homogenous patient populations: results couldn’t be generalized Intermittent HD vs CRRT  Multicentre, prospective, randomized, controlled trial  Single center, randomized, controlled trial (CONVINT)  316 adults, AKI patients  252 adult AKI patients  Mortality:  Survival rate: 39.5% IHD intermittent HD:62.5% CRRT: 58.1%  Modality of RRT has no impact on the outcome in ICU 43.9% CVVH  No significant difference regarding mortality, renal outcome measures or survival Schefold JC et al. Critical Care 2014 Rins RL et al. Nephrol Dial Transplant 2009 Intermittent HD vs CVVH  Multicenter, randomized and prospective study (21 center, Hemodiafe Study Group)  Adults with multiorgan dysfunction syndrome and AKI  Rate of survival did not differ between the intermittent HD and CVVH Vinsonneau C et al, The Lancet, 2006 Intermittent HD vs CVVH  ATN and RENAL studies suggest that CVVH might help with renal recovery  Meta-analysis studies reveals no difference in long term dialysis dependency Ghahramani N et al. Nephrology 2008 Suggested modality choice in pediatric ARF Goal of dialysis Hemodynamic status modality Ultrafiltration Normotensive hypotensive Intermittent HD (w isolated UF) Continuous HF or PD Urea clearance Normotensive hypotensive Intermittent HD or PD Continuous HF or PD Treatment of hperkalemia Either normotensive Intermittent HD or hypotensive Correction of metabolic acidosis Normotensive hypotensive Any Continuous HF or PD Treatment of Either normotensive Any; continuous hemofiltration Hyperphosphatemia or hypotensive possibly superior Flynn JT. Pediatr Nephrol 2002 RRT modality: conclusion  Few data available regarding pediatric patients  Decision: empirical  Consider:  Underlying disease  Severity of illness  Advantages and disadvantages of the various modalities available locally  Cost  Although survival was somewhat the same/better in intermittent HD group, provision of HF most likely contributed to the survival of many patients who might not survived had HF not available Maxvold NJ et al. Am J Kid Dis 1997 (abstr) Conclusion  Combination  CRRT: early correction of hemodynamic instability as long as multiorgan failure exist  Classic intermittent HD for long lasting-isolated AKI Rins RL et al. Nephrol Dial Transplant 2009 Dose of CVVH in AKI  Expression of how much dialysis should be prescribed in order to achieve a certain level of blood cleansing  Dose relies on  Patient clinical picture (catabolic rate, muscle mass, presence of pulmonary edema, fever, dysionemia etc.)  Solute to clear (water, urea, electrolytes, cytokines..)  The final desired blood level of the target solute  In CVVH (small solute) clearance is essentially considered equal to UF rate Optimal RRT dose in ICU: 2 multicenter clinical trials Compare normal or less intensive renal support to intensive therapy RENAL VA/NIH ARF trial network (ATN) study  1124 patients  1500 patients  25 ml/kg/h CVVHDF  20 ml/kg/h CVVHDF/ vs 40 ml/kg/h N England J Med, 2009 thrice weekly IHD vs 35 ml/kg/h/daily IHD N England J Med, 2009 No benefit in outcomes by increases in intensity of RRT dose Conclusion  Normal dose: 20-30 ml/kg/h for continuous therapy Ricci Z, Ronco C. Current Opinion Critical Care, 2011  Overt underdialysis might be harmful in ICU!!  Be careful about the discrepancy between prescribed and delivered dose!!! DOse REsponse Multicenter International Collaborative Initiative (DoReMi)  The difference between prescribed and delivered dose  Relies on therapy downtime (the amount of time the CRRT does not run in a 24 h period),  clotting of the circuit,  Vascular access problems  Prescription errors Crit Care 2009 When you prescribe 20-25 ml/kg/h during CRRT significant reduction in dialysis dose delivery should be considered!  In practice you may need to over- prescribe RRT with 25% of safety margin Recommendation: 30-35 ml/kg/h? Kellum JA, Ronco C Nat Rev Nephrol 2010 Ricci Z, Ronco C. Curr Opin in Crit Care, 2011 Anticoagulation  Low dose heparin  10-20 IU/kg bolus  10-20 IU/kg/h continuous drip (target activated clotting time: 180-200 s or partial tromboplastin time that is double the normal value)  Citrate anticoagulation  No anticoagulation When to stop?  No randomized controlled trials addressing this issue  Observational studies have suggested that urine output can be used to predict successful cessation of CRRT  Spontaneous urine output >500 ml/day? (adult) Uchino S et al. Crit Care Med 2009 Complications of CVVH  High cost  Technological complexity  Specialized nursing staff usually required  Hypothermia  Membrane bioincompatibility  Acid-base imbalance  Electrolyte imbalance  Removal of drugs and nutrients  Volume depletion Common in both CVVH and IHD Long-term outcomes  Mortality is high  At least 10% of children who survive AKI have evidence of  Hyperfiltration  Hypertension  Microalbuminuria Puts them at risk of long term progressive loss of kidney function  Long term follow-up is important! Early intervention with ACE inhibitors, angiotensin receptor blockers or other renoprotective therapies if necessary Askenazi DJ et al. Kidney Int 2006 Firdevs Çalkanoğlu