Rajeev Annigeri. Apollo Hospitals, Chennai. Overview of Renal Replacement Therapy (RRT) in intensive care unit (ICU). Rajeev Annigeri. Apollo Hospitals, Chennai.

Overview Indications to initiate RRT in ICU. Modes of RRT. Choosing modality of RRT. Goals of RRT. Outcomes of patients receiving RRT. Our experience over a decade.

Indications to initiate RRT in ICU. Absolute (Emergency) Standard (Dialysis) Relative (Support) Azotemia Pericarditis, encephalopathy, neuropathy (BUN>150 mg/dl) BUN > 100 mg/dl BUN > 60 mg/dl, and rising Acidosis pH < 7.1, despite corrective measures. pH < 7.2 ? <7.25 Fluid overload Refractory pulmonary edema Severe organ edema Fluid accumulation > 10% body weight despite fluid restriction and diuretic Dyselectrolytemia S. K >6.5 meq/L despite therapy S. K > 6 meq/L and rising trend despite therapy - Urine output Anuria > 24 hours despite diuretic challenge Anuria > 12 hours despite diuretic challenge

Modalities of RRT for AKI RRT in ARF Intermittent therapies Intermittent HD SLEDD Continuous therapies CVVHD PD / HVPD

How to choose the modality of RRT. CRRT PIRRT/SLED HD

Comparison of different modalities of RRT. HD SLEDD CRRT PD Blood flow (ml/min) 200-300 100-150 - Dialyzate flow (L/hr) 30 12-15 1.5-2 1-2 Duration per session (hrs) 3-5 6-8 24 Urea cl (L/session) 40 35-40 36-48 10-18

Advantages of different modalities of RRT Continuous therapies Intermittent therapies Mimics physiology. Hemodynamically well tolerated. Smooth control of uremic toxins, devoid of peaks and troughs of uremic toxins. Fluid removal is better tolerated. Does not require water treatment facility needed for Hemodialysis. Renal recovery may be better. Rapid correction of acidosis and electrolyte abnormality. Less expensive. More widely available.

Disadvantages of different modalities of RRT Continuous therapies Intermittent therapies More expensive. More labor intensive. Needs more tests for monitoring. Needs a dedicated machine. Hemodynamically less well tolerated. Fluid removal is less efficient in view of shorter duration of dialysis.

How do they rank over all? CRRT HD SLED PD/HVPD Survival 4 1 Recovery from AKI 3 Small solute Clearance Middle molecule Clearance 2 Fluid removal Acid Base control Safety Cost Ease of operation Total 32 28 31 18

When to initiate RRT in ARF in ICU? Liu et al 2006 243 Randomized trial 47.5 115 35 41 No difference in survival when RRT was initiated at BU 100 mg/dl and 200 mg/dl

Meta-analysis: Early dialysis may be beneficial in post surgical AKI. However, if segregate the studies into post surgical and heterogeneous population the studies which showed benefit were all in the post surgical group and the number of patients in these studies was rather small.

Therapeutic targets of RRT in ICU. Azotemia BUN < 60mg/dl (Blood urea < 120 mg/dl). Acidosis pH > 7.2. Abnormal electrolyte level Serum electrolytes within normal range. Accumulation of fluid Fluid removal to achieve volume closer to normal.

Dose of dialysis: Quantification. Dose is quantified by Urea Kinetic Modeling (UKM). UKM based calculations of plasma solute clearance is the most commonly used method. Solute clearance= Kt/V.

Dose of dialysis. High dose dialysis is not superior to standard dose with regard to survival. 20-25 ml/kg/hr dose in CRRT is sufficient. Kt/V of 1.0 in continuous and 1.3 in intermittent dose therapy is probably sufficient. Keep blood urea levels at 60-120 mg/dl (BUN 30-60 mg/dl).

Impact of acidosis at initiation of RRT. No clear guidelines. Rapid correction and normalization may not be desirable. No studies specifically addressing the issue in dialysis dependent AKI. pH: >7.35 pH: 7.2-7.35 pH<7.2 Unpublished data from our unit

Management of fluid balance. Large fluid accumulation of fluids in ICU is common. Fluid accumulation is an independent risk factor for development of AKI and mortality in ICU. Organ edema worsens organ dysfunction. Use of loop diuretics is justified for excessive fluid accumulation of >10%.

Mortality rate by final fluid accumulation relative to baseline weight and stratified by dialysis status. PICARD study The adjusted OR for death associated with fluid overload at dialysis initiation was 2.07.

Mortality rate by categorical percentage of dialysis days with fluid overload. Their results indicated that more the time one is in positive fluid overload the likely that they will take longer time to recover from AKI PICARD study

Relationship between dialysis modality and fluid accumulation. PICARD study

When to stop dialysis? No clear guidelines. Criteria: urine output is more than 0.5ml/kg/hour. Blood urea <200 mg/dl. Serum creatinine <6 mg/dl. No uremic symptoms. Try frusemide infusion, if fluid removal is desirable.

Follow up of AKI patients Need periodic check up, probably annually, especially if have high risk of progression to CKD. Monitor eGFR, proteinuria and blood pressure at least annually. ?Restrict salt, ? RAAS blockade if tolerated.

AKI as a risk of progression to CKD: data from large data base Half a million patients, follwed over a mean of 8 years Lo LJ, Kid Int 2009

Summary. Initiate RRT early, before absolute indications appear, if trend do not show sign of improvement. If hemodynamically unstable use CRRT as the initial mode of dialysis is expertise is available. Dose: Maintain Blood urea <120 mg/dl (BUN <60 mg/dl).

Summary. Monitor degree of azotemia, acidosis, fluid balance and electrolytes and modify RRT as needed. When hemodynamics are better switch to SLED after 2-4 days. When urine output is >500 ml/min, and serum creatinine is <5mg/dl, stop RRT and watch. Monitor closely after discharge and annual check up there after.

Renal replacement therapy in ICU: A decade of experience at Apollo Hospitals, Chennai.

AKI: Indian perspective. AKI: Epidemiology RR of death 16 (7%) were initiated on RRT. Reddy P K et al, Renal Failure 2014

Baseline characteristics of AKI patients initiated on RRT in ICU. Period 1: 2004-07 Period 2: 2008-11 Annigeri R A et al. Indian J Crit Care Med, Jan 2016

Changes in dialysis practice patterns between two periods. Introduction of prolonged intermittent RRT (PIRRT) Early dialysis for metabolic acidosis, anuria and positive fluid balance. Use of bicarbonate‑based fluids for continuous RRT (CRRT) instead of lactate buffer. Annigeri R A et al. IJCCM, Jan 2016

Hemodynamic parameters to choose RRT.   CRRT (N=109) PIRRT (N= 37) P value between CRRT and PIRRT IHD (N=16) Systolic blood pressure (mm Hg) 106.818.6 114.122.5 0.053 135.527.3 Diastolic blood pressure (mm Hg) 58.812.7 63.211.8 0.066 72.513.4 MAP (mm Hg) 74.911.9 80.112.1 0.024 93.515.6 Inotropes None 1 2 >2 11 (10%) 39 (35.8%) 34 (31.2%) 25 (23%) 14 (37.8%) 20 (54%) 2 (5.4%) 1 (2.7%) <0.001 0.055 0.002 0.005 9 (56.2%) 3 (18.8%) 4 (25%) Annigeri R A et al. IJCCM, Jan 2016

Indications for initiation of RRT. Annigeri R A et al. IJCCM, Jan 2016

Study outcomes. All patients Period-1 Period-2 p value   All patients Period-1 Period-2 p value 28-day Hospital mortality 110 (67.9%) 55 (79.7%) 55 (59.1%) 0.004 Duration of ICU stay (days) 12.413.9 11.813.8 1313.9 0.62 Dialysis dependent at discharge 4 (2.5%) 2 (2.8%) 2 (2.2%) 0.76 Annigeri R A et al. IJCCM, Jan 2016

Survival analysis 2006-2011 2004-2006 Early initiation of RRT for acidosis, anuria during period-2 may have improved outcome Annigeri R A et al. IJCCM, Jan 2016

Mortality and modality of RRT. Annigeri R A et al. IJCCM, Jan 2016

Mortality: Results of univariate and multivariate regression analysis. Annigeri R A et al. IJCCM, Jan 2016

Biomarkers to guide RRT? Urinary NGAL accurately predicts severity of AKI and dialysis need as well as mortality. If indication for dialysis is relative, high urinary NGAL (>500 ng/ml) may be an useful marker to initiate RRT, but needs to be studied formally. There is lot of excitement in recent years about the utility of biomarkers to guide therapy. One of the methods urinary NGAL may help us is to indicate severe nature of AKI and if present in the presence of relative indications for dialysis, it may be initiated with certain degree of confidence. However, this approach is not been tested clinically.

Prediction of outcomes: uNGAL Progression of AKI. Composite of dialysis and death. Data presented at ISNCON, Bengaluru December 2015

Sensitivity and specificity of different cut-off values of uNGAL Positive predictive value Negative predictive value uNGAL cut-off value 500 ng/ml PROGRESSION AKI MORTALITY DIALYSIS 44 33 41 83 84 38 81 uNGAL cut-off value 1000 ng/ml 39 43 52 85 87 89

Summary of our experience. PIRRT can be used safely in patients with mild hemodynamic instability and CRRT may be reserved for patients with more hemodynamic instability. Introduction of PIRRT resulted in 37% reduction in utilization of CRRT. Mode of RRT may not influence outcomes. Earlier initiation of RRT for indications of anuria/fluid overload and acidosis may improve outcomes. When in dilemma err on the side of starting dialysis and use uNGAL as a predictor of progression.

r_annigeri@yahoo.com