Shiraz Medical University Faghihi Hospital Dr-Ramin Radmehr Dr R - Radmehr

Sustained Low Efficacy Daily Dialysis SLEDD

TOPICS Introduction RRT in ICU (( SLED )) definition Comparison and outcome Conclusions Questions Dr R - Radmehr

Acute Kidney Injury in the ICU AKI is common : 3-35%* of admissions AKI is associated with increased mortality “Minor” rises in Cr associated with worse outcome AKI developing after ICU admission (late) is associated with worse outcome than AKI at admission. AKI requiring RRT occurs in about 4-5% of ICU admissions and is associated with worst mortality risk ** * Brivet, FG et al. Crit Care Med 1996; 24: 192-198 ** Metnitz, PG et al. Crit Care Med 2002; 30: 2051-2058 Dr R - Radmehr Dr R-Radmehr

Mortality by AKI Severity Dr R - Radmehr Clermont, G et al. Kidney International 2002; 62: 986-996 Dr R-Radmehr

RRT for Acute Renal Failure There is some evidence for a relationship between higher therapy dose and better outcome, at least up to a point -This is true for IHD* and for CVVH** There is no definitive evidence for superiority of one therapy over another, and wide practice variation exists*** Accepted indications for RRT vary No definitive evidence on timing of RRT Dr R - Radmehr Dr R-Radmehr

AKI classification systems 1: RIFLE Dr R - Radmehr Dr R-Radmehr

Proposed Indications for RRT Oliguria < 200ml/12 hours Anuria < 50 ml/12 hours Hyperkalaemia > 6.5 mmol/L Severe acidaemia pH < 7.0 Uraemia > 30 mmol/L Uraemic complications Dysnatraemias > 155 or < 120 mmol/L Drug overdose with dialysable drug Dr R - Radmehr Dr R-Radmehr

Major Renal Replacement Techniques Intermittent Hybrid Continuous CVVH Continuous veno-venous haemofiltration IHD Intermittent haemodialysis SLEDD Sustained (or slow) low efficiency daily dialysis IUF Isolated Ultrafiltration CVVHD Continuous veno-venous haemodialysis SLEDD-F Sustained (or slow) low efficiency daily dialysis with filtration CVVHDF Continuous veno-venous haemodiafiltration SCUF Slow continuous ultrafiltration Dr R - Radmehr Dr R-Radmehr

Sustained Low Efficacy Dialysis Hybrid technicque that is alternative to Intermittent Hemo Dialysis and CRRT ((SLED)) Dr R - Radmehr

Dr R - Radmehr

Intermittent hemodialysis (IHD) Advantages Disadvantages - short duration - less labour intensive - less anticoagulation ----> less bleeding - optional bicarbonate dialysate production - better in high K+ - technically difficult - requires hygienic removal of effluent - requires a fresh water supply - more electrolyte disequilibrium - cardiovascular instability - requires trained personnel Cerebral edema Hypotention Dr R - Radmehr

Intradialytic Hypotension: Risk Factors LVH with diastolic dysfunction or LV systolic dysfunction / CHF Valvular heart disease Pericardial disease Poor nutritional status / hypoalbuminaemia Uraemic neuropathy or autonomic dysfunction Severe anaemia High volume ultrafiltration requirements Predialysis SBP of <100 mm Hg Age 65 years + Pressor requirement Dr R - Radmehr

CRRT - haemodynamic stability - easy to operate Advantages Disadvantages - haemodynamic stability - easy to operate - adequate nutritional support possible - superior solute and volume control - requires anticoagulation - mobilization of patients difficult - sterile haemofiltration fluid -> cost ++ - no as good in hyperK+ as IHD Dr R - Radmehr

SLED - easy to perform - flexible timing for treatments Advantages Disadvantages - easy to perform - flexible timing for treatments - 12 hour or overnight treatments - increased patient mobility and access - procedural simplicity - clinical unfamiliarity - hypophosphataemia - unknown effects on clearance of drugs - hypothermia Dr R - Radmehr

SLED SLED - clinical unfamiliarity - hypophosphataemia Advantages Disadvantages - cardiovascular stability comparable to CRRT - small molecule clearance comparable to IHD and CRRT - less anticoagulation required (air free tubing) - composition of dialysate easily modified - clinical unfamiliarity - hypophosphataemia - unknown effects on clearance of drugs - hypothermia Dr R - Radmehr

SLED SLED - clinical unfamiliarity - hypophosphataemia Advantages Advantages Disadvantages Disadvantages - effective in hyperkalaemia - no mortality difference when compared to CRRT - able to use SLEDD-F = sustained low efficiency daily diafiltration -> removal of middle sized molecules in SIRS - clinical unfamiliarity - hypophosphataemia - unknown effects on clearance of drugs - hypothermia Dr R - Radmehr

SLED SLED Advantages Advantages Disadvantages Disadvantages - in RRT for toxins it reduces rebound intoxication after ceasing of RRT - no bag handling -> decreased infection risk - cheaper than CRRT - clinical unfamiliarity - hypophosphataemia - unknown effects on clearance of drugs - hypothermia Dr R - Radmehr

Kinetic Modelling of Solute Clearance CVVH (predilution) Daily IHD SLED Urea TAC (mg/ml) 40.3 64.6 43.4 Urea EKR (ml/min) 33.8 21.1 31.3 Inulin TAC (mg/L) 25.4 55.5 99.4 Inulin EKR (ml/min) 11.8 5.4 3.0 b2 microglobulin TAC (mg/L) 9.4 24.2 b2 microglobulin EKR (ml/min) 18.2 7.0 4.2 TAC = time-averaged concentration (from area under concentration-time curve) EKR = equivalent renal clearance Inulin represents middle molecule and b2 microglobulin large molecule. CVVH has marked effects on middle and large molecule clearance not seen with IHD/SLED SLED and CVVH have equivalent small molecule clearance Daily IHD has acceptable small molecule clearance Dr R - Radmehr Dr R-Radmehr

Continuous vs intermittent dialysis Ongoing debate Theoretical benefits to both At least 7 RCTs and 3 meta-analyses have not demonstrated difference in outcome 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). suggestion that continuous RRT had fewer episodes of hemodynamic instability and better control of fluid balance Continuous RRT is preferable in Unstable patients Recent research shows more renal recovery in Continuous espiscially CRRT Dr R - Radmehr Vanholder et al. Pro/con debate: Continuous vs intermittent dialysis for acute kidney injury. Critical Care 2011, 15:204

Continuous RRT Theoretical advantage of more hemodynamic stability allowing more adequate fluid removal 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. 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 Dr R - Radmehr Dr R-Radmehr

Conclusions SLEDD is the most flexible and cheaper 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 : Consider CRRT if severely unstable pts, severe volume overload, combined renal/hepatic failure IRRT best if bleeding risk or acute hyperkalemia/poisoning ( Stable BP ) Renal recovery in CRRT is more probable due to better perfusion status CVVH is the best in Sepsis due to its mechanism. SLEDD is the most flexible and cheaper Dr R - Radmehr

Best wishes Dr R - Radmehr