Dialysis in the Critically Ill Fellows conference Cheryl

Dialysis in the Critically Ill Fellow’s conference Cheryl Pirozzi, MD February 15, 2012 www. pyroenergen. com/. . . /dialysis-treatment. jpg

Outline p p p p p AKI in the ICU Principles of RRT Modes of RRT Indications for RRT Optimal timing: When to start and stop Optimal modality: When to use what Optimal dosing RRT in specific clinical situations Conclusions

AKI in the ICU p AKI is common in the ICU Depending on definition of AKI, up to 5060% of patients in the ICU p Up to 70% of these will require RRT p Independent risk factor for mortality, 50 - 60% mortality in critically ill p Rondon-Berrios. Curr Opin Nephrol Hypertens. 2007 Mar; 16(2): 64 -70. Foot. Current Anaesthesia and Critical Care 2005; 16: 321 -329 • Miller's Anesthesia, 7 th ed. 2009

AKI in the ICU p p p Treatment of acute kidney injury (AKI) is principally supportive -- renal replacement therapy (RRT) indicated in patients with severe kidney injury. Goal: optimization of fluid & electrolyte balance Multiple modalities of RRT : n Intermittent hemodialysis (IHD), n continuous renal replacement therapies (CRRTs) n hybrid therapies, ie sustained low-efficiency dialysis (SLED) Foot. Current Anaesthesia and Critical Care 2005; 16: 321 -329

Principles of dialysis p Dialysis = diffusion = passive movement of solutes across a semipermeable membrane down concentration gradient n p Good for small molecules (Ultra)filtration = convection = solute + fluid removal across semipermeable membrane down a pressure gradient (solvent drag) n Better for removal of fluid and medium-size molecules Faber. Nursing in Critical Care 2009; 14: 4 Foot. Current Anaesthesia and Critical Care 2005; 16: 321 -329

Principles of dialysis p p p Hemodialysis = solute passively diffuses down concentration gradient n Dialysate flows countercurrent to blood flow. n Urea, creatinine, K move from blood to dialysate n Ca and bicarb move from dialysate to blood. Hemofiltration: uses hydrostatic pressure gradient to induce filtration / convection plasma water + solutes across membrane. Hemodiafiltration: combination of dialysis and filtration. • Miller's Anesthesia, 7 th ed. 2009 • Foot. Current Anaesthesia and Critical Care 2005; 16: 321 -329

Modality of RRT p p Intermittent hemodialysis (IHD) Continuous renal replacement therapy (CRRT) Peritoneal dialysis Hybrid therapies, like SLEDD

Intermittent hemodialysis (IHD) p p Oldest and most common technique Primarily diffusive treatment: blood and dialysate are circulated in countercurrent manner n p p Also some fluid removal by ultrafiltration due to pressure driving through circuit Best for removal of small molecules typically performed 4 hours 3 x/wk or daily Foot. Current Anaesthesia and Critical Care 2005; 16: 321 -329 • Miller's Anesthesia, 7 th ed. 2009

Continuous RRT p p p Introduced in 1980 s involve either dialysis (diffusion-based solute removal) or filtration (convection-based solute and water removal) treatments in a continuous mode with slower rate of solute or fluid removal CRRT includes continuous hemofiltration, hemodialysis and hemodiafiltration, all of which can be performed using arteriovenous or venous extracorporeal circuits.

Continuous RRT p p p Continuous venous hemofiltration (CVVH): Uses blood pump to remove fluids/solutes by convection Continuous venous hemodialysis (CVVHD): Uses pump + dialysate run at low flow rate countercurrent to blood flow n Slower fluid removal but greater solute removal Continuous venous hemodiafiltration (CVVHDF): combines diffusion for small solute removal + convection for large solutes n Large volume filtered fluid → Requires replacement fluid n Most commonly used modality at the U

Continuous RRT p Arteriovenous versions (CAVH, CAVHD and CAVHDF) are similar to venous except use AV access and systemic BP to run and blood pump not required. n Downsides: requires arterial cannulation (+ venous) n Unreliable flow in pts with ↓ BP or severe PVD n Requires more anticoagulation n VV preferred due to lower risk, only one dual lumen catheter, and faster/more reliable flow

Slow continuous ultrafiltration (SCUF): p p p used for fluid removal in overloaded CHF patients blood is driven through a highly permeable filter in a venous mode to primarily remove water, not solute. The ultrafiltrate produced during membrane transit is not replaced so it corresponds to the fluid loss. • Miller's Anesthesia, 7 th ed. 2009

Peritoneal dialysis p p p p Least useful form of CRRT in the ICU diffusive treatment: blood in capillaries of peritoneal membrane exposed to dialysate in abdomen continuous or intermittent Inefficient solute/volume clearance if unstable or poor intestinal blood flow Can’t use if intraabdominal pathology- risk of peritonitis Respiratory burden Only two RCTs comparing to hemodialysis in AKI: found inferior or no difference Vanholder. Critical Care 2011; 15: 204 Foot. Current Anaesthesia and Critical Care 2005; 16: 321 -329

Sustained low-efficiency daily dialysis (SLEDD) p p p AKA Extended daily dialysis (EDD) or slow continuous dialysis (SCD) Hybrid therapy: IRRT at lower blood and dialysate flows for prolonged times (Usually ≥ 5 hrs) Uses conventional dialysis machines Flexibility of duration and intensity Major advantages: flexibility, reduced costs, low or absent anticoagulation Used at IMC but not U due to tech/nurse training

Anticoagulation p p p CRRT requires continuous anticoagulation to prevent clotting in the CRRT circuit Tricky bcs ICU pts often at increased risk of bleeding and hypercoagulable Many options: n Systemic anticoagulation with heparin (mst common), LMWH, heparinoids, thrombin antagonists n Regional citrate anticoagulation (preferred) n Other regional anticoagulation ie heparin/protamine Davenport. NDT Plus (2009) 2: 439– 447

Regional citrate anticoagulation p p Citrate infused into the blood at the start of the circuit provides anticoagulation by chelating i. Ca++ Requires systemic Ca infusion to replace Ca lost with citrate target extracorporeal blood citrate 4– 6 mmol/l, prefilter i. Ca++ <0. 35 mmol/l Davenport. NDT Plus (2009) 2: 439– 447

Regional citrate anticoagulation p Advantages of RCA for CRRT: n n p avoids systemic anticoagulation (lower bleeding risk) and heparin risks (HIT) act as a buffer by conversion through to bicarbonate Disadvantages: n n n potential metabolic complications: metabolic acidosis/alkalosis, hypo. Ca, Hyper. Na, hypo. Mag complex protocols-- q 6 h monitoring of Na, K, Cl, i. Ca++, Mg, ABG, AG More expensive Davenport. NDT Plus (2009) 2: 439– 447

Indications for RRT p p p Acute management of life-threatening complications of AKI: A: Metabolic acidosis (p. H less than 7. 1) E: Electrolytes -- Hyperkalemia (K >6. 5 meq/L) or rapidly rising K) I: Ingestion -- Certain alcohol and drug intoxications O: Refractory fluid overload U: Uremia, ie. pericarditis, neuropathy, decline in mental status

Timing of initiation of RRT p p p p Unclear if earlier RRT is better Theoretical benefits: may attenuate organ injury from acidemia, uremia, fluid overload, and systemic inflammation Several non-randomized studies have reported improved outcomes (incl survival), associated with early RRT One RCT: Bouman Crit Care Med. 2002; 30(10): 2205 106 ICU pts with UOP < 30 x 6 hrs and Cr. Cl <20 assigned to early (≤ 12 hrs) high- or low- volume CVVH, vs late (BUN 40 mmol/L, K 6. 5 mmol/L or severe pulmonary edema) low-volume CVVH→ Survival at 28 days and recovery of renal fcn equivalent. However, underpowered

Timing of initiation of RRT p p p Karvellas. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury. Critical Care 2011, 15: R 72 Meta-analysis of 15 studies Early RRT initiation associated with ↓mortality (pooled OR 0. 45) However, significant heterogeneity and bias Some studies showed greater renal recovery, ↓ duration RRT and ICU length of stay

Timing of initiation of RRT p p p Earlier initiation of RRT in critically ill patients with AKI may have a beneficial impact on survival and outcomes but data is insufficient Many recommend initiation of RRT prior to the development of advanced uremic symptoms, or when the BUN reaches 80 - 100 mg/d. L No known threshold of fluid overload for initiating RRT

Discontinuation of RRT p Until “evidence of recovery of kidney function” n n n Improved UOP in oliguria Decreasing creatinine Creatinine clearance minimum 12 m. L/min, some say 20 m. L/min

Continuous vs intermittent dialysis p p Ongoing debate Theoretical benefits to both At least 7 RCTs and 3 meta-analyses have not demonstrated difference in outcome n Eg Bagshaw Crit Care Med 2008, 36: 610 -617: metaanalysis of 9 randomized trials: No effect on mortality (OR 0. 99) or recovery to RRT independence (OR 0. 76). n suggestion that continuous RRT had fewer episodes of hemodynamic instability and better control of fluid balance May be preferable in specific subpopulations Vanholder et al. Pro/con debate: Continuous vs intermittent dialysis for acute kidney injury. Critical Care 2011, 15: 204

Pro-continuous RRT ? Theoretical advantage of more hemodynamic stability allowing more adequate fluid removal p p p Metaanalysis of 15 RCTs (Rabindranath Cochrane Rev 2007, 3): no difference between CRRT and IRRT in haemodynamic instability or hypotension / escalation of pressors, or mortality or RRT independence. n Patients on CRRT had significantly higher MAP However most trials excluded pts with major hemodynamic issues Some RCTs (but not all) show more negative fluid balances with CRRT vs IRRT Vanholder et al. Critical Care 2011, 15: 204

Pro-continuous RRT p ? Better recovery of renal function due to preserved hemodynamic stability n p All RCTs and meta-analyses have failed to show superiority of CRRT in progression to CKD or RRT dependence ? Improved solute removal due to longer dialysis n n Studies have been inconsistent in showing improved clearance of creatinine and urea with CRRT No evidence of improved removal of cytokines Vanholder et al. Critical Care 2011, 15: 204

Pro-continuous RRT p Specific patient populations who may benefit from CRRT n n n Hemodynamic instability Combined acute renal and hepatic failure p Improved CV instability and intracranial pressure Acute brain injury p Decreased cerebral edema Vanholder et al. Critical Care 2011, 15: 204

Pro-intermittent RRT p Practicality and flexibility n n n p p Less expensive than CRRT (by about ½) Fewer bleeding complications n p p Uses same machines as chronic HD Multiple pts per day Easier to mobilize pts CRRT requires continuous anticoagulation Less filter clotting Superior solute clearance, more rapid removal of toxins (due to higher flows) Vanholder et al. Critical Care 2011, 15: 204

Pro-intermittent RRT p Specific patient populations benefitting from IRRT: n n High bleeding risk p Ie. after recent surgery Acute treatment of hyperkalemia, rhabdomyolysis, poisoning, tumor lysis syndrome Vanholder et al. Critical Care 2011, 15: 204

Is SLEDD the answer? p p Hybrid therapy with flexibility of duration and intensity SLEDD vs CRRT Major advantages: flexibility, reduced costs, low or absent anticoagulation Similar adequacy and hemodynamics n n One small study (16 pts) showed slightly higher acidosis and lower BP (Baldwin 2007) VA trial (Palevsky NEJM 2008) suggests similar outcomes as CRRT and IRRT. Vanholder et al. Critical Care 2011, 15: 204

Optimal dosing p p p Optimal intensity of RRT is controversial VA/NIH Acute Renal Failure Trial Network. (NEJM 2008; 359: 7): RCT of 1124 critically ill pts with AKI and sepsis or at least one organ failure to intensive or less intensive renal-replacement therapy Hemodynamically unstable pts received CRRT or SLEDD, stable pts IRRT Intensive RRT= IRRT or SLEDD 6 x/wk or CRRT at 35 ml/kg/hr Less intensive RRT= IRRT or SLEDD 3 x/wk or CRRT at 20 ml/kg/hr

Optimal dosing p p VA/NIH Acute Renal Failure Trial Network No difference in mortality, recovery of kidney function, or nonrenal organ failure VA/NIH Acute Renal Failure Trial Network. NEJM 2008; 359: 7

Optimal dosing p p p The RENAL Replacement Therapy Study RCT of 1508 critically ill pts to CRRT of high vs low intensity (40 vs 25 ml/kg/hr) No difference in 90 d mortality or RRT independence N Engl J Med. 2009 Oct 22; 361(17): 1627 -38

Optimal dosing p p p Recommended dosing: IRRT: 3 x/week CRRT: delivered effluent flow rate of at least 20 m. L/kg/hr Up To Date. com

The role of RRT in different clinical situations p p Sepsis and MODS Congestive heart failure • Miller's Anesthesia, 7 th ed. 2009

RRT in sepsis/MODS RRT has been proposed as a “Extracorporeal blood purification therapy (EBPT)” as adjuvant therapy for sepsis/MODS for removal of harmful inflammatory mediators or endotoxemia p Some support from animal models and small clinical studies p n Eg cytokines can be demonstrated in dialysis effluent • Miller's Anesthesia, 7 th ed. 2009 Foot. Current Anaesthesia and Critical Care 2005; 16: 321 -329

RRT in sepsis/MODS p p Limited data, small studies: Cole. Crit Care Med. 2002 Jan; 30(1): 100 -6 n Phase II RCT of early CVVH x 48 h in 24 pts with septic shock/MODS n No ↓ in circulating cytokines and anaphylatoxins or organ dysfunction

RRT in sepsis/MODS p Limited data, small studies: p Boussekey et al. Intensive Care Med. 2008 Sep; 34(9): 1646 -53 Pilot RCT of 20 pts with septic shock and ARF to high volume hemofiltration [HVHF 65 ml/(kg h)] vs low volume hemofiltration [LVHF 35 ml/(kg h). HVHF decreased vasopressor requirement and trend towards increase urine output but no effect on survival, LOS, RRT, mech ventilation p p

RRT in sepsis/MODS Overall, no good data showing improved outcomes p Insufficient evidence to support a role for RRT as adjuvant therapy for septic shock unless severe acute renal failure is present. p Foot. Current Anaesthesia and Critical Care 2005; 16: 321 -329

RRT in congestive heart failure p p Slow continuous ultrafiltration (SCUF) effective for fluid removal in decompensated CHF UNLOAD trial (UF versus intravenous diuretics for acute decompensated CHF): n RCT 200 hypervolemic CHF pts to UF or diuretics n At 48 hrs, UF associated with improved weight and fluid removal, and ↓ 90 d rehospitalization and medical visits for CHF • Costanzo et al J Am Coll Cardiol 2007; 49: 675 -683.

Conclusions p p p AKI in the ICU is common and associated with high mortality The best time to initiate and stop RRT is controversial No good data that CRRT is better than IRRT in the ICU, except for a few specific situations n Consider CRRT if severely unstable pts, severe volume overload, combined renal/hepatic failure n IRRT best if bleeding risk or acute hyperkalemia/poisoning n SLEDD is the most flexible

Conclusions p p p More intense RRT dosing in the ICU does not improve outcome Insufficient evidence to support a role for RRT as adjuvant therapy for septic shock unless severe acute renal failure is present Ultrafiltration is effective for fluid removal in CHF

References p p p p Miller: Miller's Anesthesia, 7 th ed. 2009 Uchino S, Kellum JA, Bellomo R, et al: for the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 2005; 294: 813 -818. Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, Zandstra DF, Kesecioglu J. Effects of early high-volume continuous venous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial. Crit Care Med. 2002; 30(10): 2205. Vanholder et al. Pro/con debate: Continuous vs intermittent dialysis for acute kidney injury. Critical Care 2011, 15: 204 Uchino S, Bellomo R, Morimatsu H, et al: Continuous renal replacement therapy: A worldwide practice survey: The Beginning and Ending Supportive Therapy for the Kidney (B. E. S. T. Kidney) Investigators. Intensive Care Med 2007; 33: 1563 -1570. Bagshaw SM, Berthiaume LR, Delaney A, Bellomo R: Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a meta-analysis. Crit Care Med 2008, 36: 610 -617. Rabindranath K, Adams J, Macleod AM, Muirhead N: Intermittent versus continuous renal replacement therapy for acute renal failure in adults. Cochrane Database Syst Rev 2007, 3: CD 003773.

References p p p p Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM; Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P: Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008, 359: 7 -20. RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, Mc. Arthur C, Mc. Guinness S, Myburgh J, Norton R, Scheinkestel C, Su S. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009 Oct 22; 361(17): 162738. Rondon-Berrios H, Palevsky PM. Treatment of acute kidney injury: an update on the management of renal replacement therapy. Curr Opin Nephrol Hypertens. 2007 Mar; 16(2): 64 -70. Palevsky P. Renal replacement therapy (dialysis) in acute kidney injury (acute renal failure) in adults: Indications, timing, and dialysis dose. Up. To. Date. com 2012 Boussekey N, Chiche A, Faure K, Devos P, Guery B, d'Escrivan T, Georges H, Leroy O. A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock Intensive Care Med. 2008 Sep; 34(9): 1646 -53. Cole L, Bellomo R, Journois D, et al: High-volume hemofiltration in human septic shock. Intensive Care Med 2001; 27: 978 -986. Cole L, Bellomo R, Hart G, et al: A phase II randomized, controlled trial of continuous hemofiltration in sepsis. Crit Care Med 2002; 30: 100 -106.

References p p p Costanzo MR, Guglin M, Saltzberg MT, et al: for the UNLOAD Trial Investigators: Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol 2007; 49: 675 -683. Ronco C, Brendolan A, Lonnemann G, et al: A pilot study of coupled plasma filtration with adsorption in septic shock. Crit Care Med 2002; 30: 1250 -1255. Carole L. Foot, John F. Fraser. So you need to start renal replacement therapy on your ICU patient? Current Anaesthesia & Critical Care (2005) 16, 321– 329 Peter Faber and Andrew A Klein. Acute kidney injury and renal replacement therapy in the intensive care unit. Nursing in Critical Care 2009; 14: 4 Davenport A, Tolwani A. Citrate anticoagulation for continuous renal replacement therapy (CRRT) in patients with acute kidney injury admitted to the intensive care unit. NDT Plus (2009) 2: 439– 447

p p Surviving sepsis 2008: D. Renal Replacement 1. We suggest that continuous renal replacement therapies and intermittent hemodialysis are equivalent in patients with severe sepsis and acute renal failure (grade 2 B). 2. We suggest the use of continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients (grade 2 D

AKI in the ICU p In BEST Kidney trial: multinational observational trial of 29, 269 ICU patients with AKI [oliguria (UOP < 200/12 h, azotemia (BUN > 30) or RRT] n 5. 7% had AKI during their ICU stay n 4. 3% treated with RRT n 47. 5% due to septic shock n 30% had preadmission CKD n Overall hospital mortality 60. 3%. Of survivors, 13. 8% dialysis dependent at discharge n Independent risk factors for hospital mortality included the use of vasopressors, mechanical ventilation, septic shock, cardiogenic shock, and hepatorenal syndrome. • Uchino JAMA 2005; 294: 813 -818. • Miller's Anesthesia, 7 th ed. 2009