Acute Hemodialysis & CRRT in AKI Paweena Susantitaphong,MD,MS1-3 1Physician Staff , Division of Nephrology, Department of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 2 International Society of Nephrology (ISN) fellowship 3Adjunct Instructor of Tufts University School of Medicine, Boston, USA.

Background DEFINITION Acute Renal Failure  Acute Kidney Injury An abrupt (within 48h) reduction in kidney function Currently defined as an absolute increase in sCr of either ≥ 0.3 mg/dl or a percentage increase of ≥ 50% or a reduction in Urine Output (documented oliguria of < 0.5 cc/kg per h for > 6 h) Crit Care 2007;11:R31

Staging of AKI : KDIGO Stage Serum creatinine Urine output 1 1.5–1.9 times baseline OR ≥ 0.3 mg/dl (≥ 26.5 mmol/l) increase < 0.5 ml/kg/h for 6–12 hours 2 2.0–2.9 times baseline < 0.5 ml/kg/h for ≥12 hours 3 3.0 times baseline OR Increase in serum creatinine to ≥ 4.0 mg/dl (≥353.6 μmol/l) OR Initiation of renal replacement therapy OR, In patients < 18 years, decrease in eGFR to < 35 ml/min per 1.73 m2 < 0.3 ml/kg/h for ≥ 24 hours OR Anuria for ≥12 hours

World Incidence of Acute Kidney Injury : A Meta-Analysis Susantitaphong P, et al. CJASN 2013, June 6

Susantitaphong P, et al. CJASN 2013, June 6

Susantitaphong P, et al. CJASN 2013, June 6 No. studies 154 112 108 108 189 No. subjects 3,585,911 3,303,992 3,281,715 3,281,715 29,400,495 Susantitaphong P, et al. CJASN 2013, June 6

Susantitaphong P, et al. CJASN 2013, June 6 No. studies 110 26 25 25 31 No. subjects with AKI 429,535 8,226 42,354 42,354 6,534 Susantitaphong P, et al. CJASN 2013, June 6

Susantitaphong P, et al. CJASN 2013, June 6 No. studies 92 21 20 20 20 No. subjects with AKI 405,616 90,048 40,631 38,914 4,427 No. subjects without AKI 1,765,574 1,127,070 1,120,523 1,120,523 127,969 Susantitaphong P, et al. CJASN 2013, June 6

Acute Kidney Injury Increases Risk of ESRD among Elderly Ishani A ,et al. J Am Soc Nephrol 2009; 20: 223–228

Risk of ESRD Coca SG, et al. AJKD 2010

Acute Kidney Injury Associates with Increased Long-Term Mortality Lafrance JP ,et al. J Am Soc Nephrol 2010;21 :345-52

Renal Replacement Therapy Timing of initiation early VS late

Indications in Renal Failure 1. Uremia impaired nutrition N/V poor appetite gastritis with UGIB, ileus, colitis Altered mental status Pericarditis (urgent indication) Bleeding from platelet dysfunction (urgent indication)

Indications 2. Refractory or progressive fluid overload 3. Uncontrollable hyperkalemia 4. Severe metabolic acidosis esp. oliguria 5. Steady worsening of renal function BUN > 70-100 mg/dl

Outcome of Early vs. Late RRT in AKI Authors Year Design N Pre-RRT BUN Survival benefit Mode of RRT Early Late Parsons et al 1961 Retro 33 120-150 >200 + HD Fischer et al 1966 162 ~150 Kleinknecht 1972 500 <93 >163 Conger 1975 Pro 18 70 150 Gillum et al 1986 34 60 100 ± Gettings et al 1999 <60 >60 CRRT Bouman et al 2002 106 47 105 CVVH Demirkilic et al 2004 61 CVVHD Elahi et al 64 Liu et al 2006 243 <76 >76 HD and CRRT The 3 retrospective observational studies from the 1960s through the early 1970s compared ‘early’ hemodialysis, as defined by BUN from <93 mg/dl to 150 mg/dl, to ‘late’ hemodialysis, as defined by BUN levels of 163 mg/dl to > 200 mg/dl. These studies all demonstrated improved survival with earlier hemodialysis. Later, there were two small prospective clinical trials. In the first trial studied in 18 patients. Early ,BUN at <70 mg/dl, and late dialysis, BUN 150 mg/dl. Survival was significant higher in the early treatment group. The second study, 34 patients. Mortality was higher in the late dialyzed group; however, given the small sample size, this difference was not statistically significant.   The next study is a retrospective study in post-traumatic AKI patients. Significant benefit favor the early group. Bouman randomized 106 critically ill patients with AKI to three groups: No significant differences in survival were observed between early and late dialysis. In addition, as a result of the small sample size. Next 2 retrospective showed the benefit of early dialysis

a historic control group). Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL We identified 23 studies (5 randomized or quasi-randomized controlled trials, 1 prospective and 16 retrospective comparative cohort studies, and 1 single-arm study with a historic control group). By using meta-analysis of randomized trials, early RRT was associated with a nonsignificant 36% mortality risk reduction (RR, 0.64; 95% CI, 0.40 to 1.05; P = 0.08). Conversely, in cohort studies, early RRT was associated with a statistically significant 28% mortality risk reduction (RR, 0.72; 95% CI, 0.64 to 0.82; P < 0.001). The overall test for heterogeneity among cohort studies was significant (P = 0.005). However, early dialysis therapy was associated more strongly with lower mortality in smaller studies (n < 100) by means of subgroup analysis. Am J Kidney Dis. 2008 Aug;52(2):272-84.

Am J Kidney Dis. 2008 Aug;52(2):272-84. Effect of early renal replacement therapy (RRT) initiation on non-recovery of renal function in AKI Am J Kidney Dis. 2008 Aug;52(2):272-84.

Solute level (Blood urea nitrogen, serum creatinine) Parameters that were used in studies for classify early and late renal replacement therapy initiation in AKI Clinical symptoms Solute level (Blood urea nitrogen, serum creatinine) Interval between ICU/hospital admission and renal replacement therapy initiation Days between biochemical diagnosis of AKI and renal replacement therapy initiation Severity of AKI (AKIN/RIFLE) classification Prognostic scores Number of organ failure

Renal Replacement Therapy Timing of initiation early VS late Modality of RRT Intermittent VS Continuous

Dialysis : Modality Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?)

Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?) Dialysis : Modality Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?) Intermittent Vs Continuous (IHD,SLED vs. CRRT?) Note IHD Intermittent Hemodialysis SLED Sustained Low-Efficiency Dialysis CRRT Continuous Renal Replacement Therapy

RRT Modalities INTERMITTENT CONTINUOUS IHD SLED/EDD CRRT SCUF CAVH CVVH CAVHD CVVHD CAVHDF CVVHDF RRTs for ARF can be classified as intermittent or continuous, based on the duration of treatment. The duration of each intermittent therapy is less than 24 hours, whereas the duration of continuous therapy is at least 24 hours.

Mechanism of clearance Hemodialysis = Diffusion Hemofiltration = Convection Hemodiafiltration = Diffusion + Convection

Diffusion Concentration gradient Molecular weight: speed & size t = equilibrium Diffusion Concentration gradient Molecular weight: speed & size Membrane resistance: membrane & unstir fluid layer

Ultrafiltration (Convection) T = later Ultrafiltration (Convection)

Intermittent Hemodialysis Dialysis : Modality Intermittent Hemodialysis

Sustained Low-Efficiency Dialysis (SLED) Dialysis : Modality Sustained Low-Efficiency Dialysis (SLED) 6-12 hrs Hemodialysis in ARF patient Long duration 6-12 hrs Dialysate flow 70-300 ml/min Critically-ill patient

Continuous Renal Replacemet Therapy (CRRT) Dialysis : Modality Continuous Renal Replacemet Therapy (CRRT)

Renal Replacement Therapy : Modality Continuous Renal Replacemet Therapy (CRRT) Separated system Automated system And finally we have the continuous therapies call continuous renal replacement therapy that might apply with the separated system which cheaper to operate or automated system with automated machine.

This picture demonstrate the separated CRRT system Separated CVVH system

: A one-year prospective observational study , 192 critically ill patients with AKI. : Separated system CVVH with the pre-dilution. Mean CVVH dose of 34.9±2.7mL/kg/h. : The APACHEII score was 23.2±8.4 and the SOFA was 12.0±4.3. : No complications. The survival rate was 32.3%. Conclusion: Separated system CVVH is simple, safe, and efficient and could provide cheaper treatments than the integrated system. It could thus be an effective, alternative treatment for critical acute kidney injury patients when the integrated mode is unavailable

This picture demonstrate the automate CRRT system Automated CVVH system

Renal Replacement Therapy : Modality PD (24 hrs) IHD (4 hrs) SLED ( 6-12 hrs) CRRT Solute removal per day + +++ Hemodynamic stability best poor Fair-good good Cost person and time ++ Complication -Infection -high sugar -visceral trauma BP drop - Air embolism - BP drop Each treatment suit for different conditions of the patients. In theory, PD is friendly for cardiovascular instability condition but the efficacy is quite limited. Intermittent hemodialysis provide high efficiency but effect cardiovascular condition. Continuous treatment and hybrid therapy such as SLED seem to be combine the benefits of both treatment.

Slow continuous ultrafiltration (SCUF) Modality of CRRT Slow continuous ultrafiltration (SCUF) Continuous arteriovenous hemofiltration (CAVH) Continuous venovenous hemofiltration (CVVH) Continuous arteriovenous hemodialysis (CAVHD) Continuous venovenous hemodialysis (CVVHD) Continuous arteriovenous hemodiafiltration (CAVHDF) Continuous venovenous hemodiafiltration (CVVHDF) The terminology for calling variety of modality of CRRT comprises of C for continuous. Next is the type of vascular access that currently uses venovenous type using double lumen hemodialysis catheter. Vascular access

Modality of CRRT Slow continuous ultrafiltration (SCUF) Continuous venovenous hemofiltration (CVVH) Continuous venovenous hemodialysis (CVVHD) Continuous venovenous hemodiafiltration (CVVHDF) Last words describes the mode of solute clearance included three cptions: hemofiltration, hemodialysis, and hemodiafiltration. Vascular access Mechanism of Clearance

SCUF Slow Continuous Ultra-Filtration Arteriovenous or venovenous Measuring device Filtrate Slow Continuous Ultra-Filtration Arteriovenous or venovenous QUF 100 – 300 mL/day Perform to maintain fluid balance, no significant convective clearance No replacement fluid

CVVH Continuous Veno-Venous HemoFiltration Veno-venous circuit Replace-ment fluid Measuring device Filtrate Continuous Veno-Venous HemoFiltration Veno-venous circuit High permeable membrane Typical UF rate 1 – 2 L/h Requires at least a blood pump (Flow > 50 ml/min) required Replacement fluid (pre-dilution VS post-dilution) UF rate is the major determinant of convective clearance. The UF rate is determined by the TMP, water permeability, pore size, surface area, and membrane thickness.

CVVHD Continuous Veno-Venous HemoDialysis High permeable membrane Dialysate Measuring device Filtrate Continuous Veno-Venous HemoDialysis High permeable membrane At least a Blood pump and a pump for Dialysate (10-30 ml/min or 1-2.5 L/h) required No replacement fluid UF for volume control, some convective clearance at high rate The dialysate flow rate is slower than the blood flow rate, allowing small solute to equilibrate completely between the blood and dialysate. As a result, the dialysate flow rate approximates urea and Cr clearance.

CVVHDF Continuous VenoVenous HemoDiaFiltration High permeable membrane Dialysate Replace-ment fluid Measuring device Filtrate Continuous VenoVenous HemoDiaFiltration High permeable membrane Ultrafiltration flow > 6 ml/min (9-12 L/day) 1 pump for dialysate (10-30 ml/min or 1-2.5 L/h)) Replacement fluid

Continuous Renal Replacement Therapy Volume Control Diffusive Clearance Convective Clearance Volume Replacement SCUF Yes - + No CVVH +++ CVVHD CVVHDF ++

IHD CRRT

Mortality RCT < 0.02 NS 0.72 Meta-analysis (Relative risk) Study N Mode of RRT ICU hospital mortality P-value Hospital mortality Comments RCT Mehta, 200132 166 CRRT/IHD 59.5% vs 41.5% <0.02 65.5% vs 47.6% < 0.02 Unexplained randomization problems Augustine 200433 80 CVVHD/IHD NA 67.5% vs 70% NS Underpowered Inadequate delivered dose of dialysis Uelinger 200534 125 CVVHDF/IHD 34% vs 38% 0.71 47% vs 51% 0.72 Enrollment problems Underpowered Vinsonneau 200635 360 60 day mortality 32.6% vs 31.5% ,p =0.98 Changes in dialysis dose Underpowered Lins 200936 316 58.1% vs 62.5% Meta-analysis (Relative risk) Tonelli ,200237 >600 0.96 Used different types of mortality Kellum , 200238 1,400 0.93 After adjustment for study quality and severity of illness, mortality was lower in CRRT patients Rabindranath, 200739 1,550 1.06 1.01 Cochrane meta-analysis Pannu ,200840 6,058 1.1 Systematic review

Renal recovery Study N Mode of RRT Definition of renal outcome Outcome P-value Comments Cohort Jacka , 200541 93 IHD/CRRT Dialysis dependence at discharge 64.3% vs 12.5% 0.0003 Higher severity score in CRRT group ,200742 2,202 Requirement of chronic dialysis after 90 days 16.5% vs 8.3% NA Higher long-term mortality in IHD vs CRRT ; after 10 yrs total risk of ESRD almost the same in both groups Uchino,200743 1,218 Dialysis dependence at hospital discharge 33.8% vs 14.5% <0.0001 Results remained significant in patients without prior CKD RCT Mehta ,200132 166 1) Dialysis dependence at hospital discharge 2)CKD at hospital discharge and dealth 1) 7% vs 14% 2) 17% vs 4% 1) NS 2) 0.01 The percentage of CKD in baseline (≥2mg/dL) was higher in patients with IHD (NS) Augustine,200433 80 Discontinuation of dialysis at discharge 4 pts vs 5 pts NS Small number of patients Uehlinger,200534 125 IHD/CVVHDF 1) Rate of dialysis dependence 2) Absence of renal recovery 1) 1pt vs 1pt 2) 58% vs 50% 1) NA 2) 0.61 Similar proportions of patients with CKD at baseline Vinsonneau,200635 360 1) Rate of renal recovery at ICU discharge 2) Rate of renal recovery at hospital discharge 1)90% vs 93% 2) 100 vs all but 1patient 1) 0.5 2) NA Not possible to determine difference in proportion of patients with CKD in the 2 groups Meta-analysis Rabindranath, 200739 1,550 number of surviving patients not requiring RRT RR=0.99 Cochrane meta-analysis Pannu ,200840 6,058 chronic dialysis RR=0.91 Systematic review

Indication for CRRT Cardiovascular failure Hypercatabolism Cerebral edema Liver failure Sepsis Adult respiratory distress syndrome Cardiopulmonary bypass Crush syndrome

Renal Replacement Therapy Timing of initiation early VS late Modality of RRT Intermittent VS Continuous Dose of RRT Daily vs AD

Dialysis Dose Measurements The treatment dose of RRT can be defined by various aspects Efficiency Intensity Frequency Clinical efficacy Ricci Z & Ronco C: Crit Care Clin 2005.

Efficiency of RRT (Clearance, K) Clearance (ml/min) Efficiency of RRT can be represented by clearance (K). K (clearance) represents only the amount of treatment per unit of time. K cannot be employed to compare various modalities differing in treatment duration. K represents an instantaneous measurement, and it correlates with the amount of solute removal at the time point of the measurement. Pisitkun et al. Contr Nephrol 2004.

Daily clearance (ml/day) Intensity of RRT (Kt) Daily clearance (ml/day) Intensity of RRT can be described by the product of clearance x time (Kt). Because the time is accounted, Kt is more effective than K in the comparison of various RRT modalities. 24h 8h 3h Pisitkun et al. Contr Nephrol 2004.

Weekly Clearance of RRT Weekly Clearance (ml/week) Frequency is an essential factor to further describe treatment dose in different modalities. Thus weekly clearance, intensity x frequency (Kt x treatment d/wk), is superior to Kt because it offers the comparison of different modalities in the more extensive view. 24h 8h 8h 3h 3h Continuous Alt.days x7 days x3 days x7 days Pisitkun et al. Contr Nephrol 2004.

Effect of Delivered RRT Dose : CRRT “Effects of different doses in CVVH on outcomes of ARF” 100 90 Overall 80 70 60 50 40 We turn to CRRT. This is a study published by Claudio Ronco in 2000. 425 patients randomized to CVVH at 20, 35, or 45 mL/kg/hr of ultrafiltration rate and you can see the step-up in survival from 41% to 57% and 58% with the 2 higher doses of therapy. 30 20 10 20 ml/kg/hr 35 ml/kg/hr 45 ml/kg/hr RCT, n=425 Ronco C. , et al. The LANCET 2000

Effect of Delivered RRT Dose : CRRT “Effects of different doses in CVVH on outcomes of ARF” 100 90 Overall Septic patients 80 70 60 50 40 When looking in subgroup of septic patient. The significant improving in survival was seen only in 45 ml/kg/hr group. 30 20 10 20 ml/kg/hr 35 ml/kg/hr 45 ml/kg/hr RCT, n=425 Ronco C. , et al. The LANCET 2000

Effect of Delivered RRT Dose : CRRT “Effects of different doses in CRRT on outcomes of ARF” UF/Dialysis 24/18 ml/kg/hr UF/Dialysis 25/0 ml/kg/hr Similar results were shown in this study by Saudan et al. that looked at CVVH of 25 mL/kg/hr or continuous hemodiafiltration with ultrafiltration at 24 mL/kg/hr and then the addition of dialysate flow at 18 mL/kg/hr. The higher dose resulted in better survival. RCT, n=206 Saudan P, et al. Kidney Int 2006; 70:1312-7

Effect of Delivered RRT Dose : CRRT Then most recently, the ATN study from US. 1124 patients were randomized to a strategy that used intermittent therapy in hemodynamically stable patients and either continuous therapy or hybrid therapies in unstable patients at two different dosing strata. So in the high-dose arm, the intensive arm patients received 6 days a week hemodialysis with a delivered Kt/V of 1.3 per treatment or continuous therapy at 35 mL/kg/hour or SLED on a 6 days a week basis. Less intensive arm, it was 3 times a week intermittent hemodialysis or hybrid therapy or CVVHDF at 20 mL/kg/hour. There was absolutely no difference in the outcome between the two treatment arms: intensive 53.6% and less intensive 51.5%. So, what does that tell us about dose and survival? Certainly, there is a relationship between dose and survival. If we don't dialyze patients with renal failure, we know they die. So we know that if we give no dose, there is very little survival. There appears to be a graded relationship in certain settings. Because, there were still some different in the dose of the higher dose group between each study such as the ATN study use predilution CVVHD while in Ronco trial used post dilution CVVH that was more effective. So what is the plateau point when increasing dose does not provide any further benefit still need to answer. There is actually other 2 studies that is going to answer this question . First from Australia randomized 1500 patients to either 25 or 40 mL/kg/hour of continuous therapy. And another study RCT, n=1124

Effect of Delivered RRT Dose : CRRT Then most recently, the ATN study from US. 1124 patients were randomized to a strategy that used intermittent therapy in hemodynamically stable patients and either continuous therapy or hybrid therapies in unstable patients at two different dosing strata. So in the high-dose arm, the intensive arm patients received 6 days a week hemodialysis with a delivered Kt/V of 1.3 per treatment or continuous therapy at 35 mL/kg/hour or SLED on a 6 days a week basis. Less intensive arm, it was 3 times a week intermittent hemodialysis or hybrid therapy or CVVHDF at 20 mL/kg/hour. There was absolutely no difference in the outcome between the two treatment arms: intensive 53.6% and less intensive 51.5%. So, what does that tell us about dose and survival? Certainly, there is a relationship between dose and survival. If we don't dialyze patients with renal failure, we know they die. So we know that if we give no dose, there is very little survival. There appears to be a graded relationship in certain settings. Because, there were still some different in the dose of the higher dose group between each study such as the ATN study use predilution CVVHD while in Ronco trial used post dilution CVVH that was more effective. So what is the plateau point when increasing dose does not provide any further benefit still need to answer. There is actually other 2 studies that is going to answer this question . First from Australia randomized 1500 patients to either 25 or 40 mL/kg/hour of continuous therapy. And another study RCT, n=1508 NEJM 2009

Effect of Dialysis Dose on Survival in Critically Ill Patients Requiring RRT 100- 90- 80- 70- 60- 50- 40- 30- 20- 10- 0- High RRT Dose Survival % Critically ill patients requiring RRT were stratified for disease severity: dialysis dose did not affect outcome in patients with very high or very low scores, but correlate with survival in patients with intermediate degree of illness. Low RRT Dose Severity of Disease Paganini et al: Blood Purif 2001.

Anticoagulation Drugs Advantages Disadvantages Heparin Good anticoagulation Thrombocytopenia , Bleeding Regional heparin Reduced bleeding Complex management LMWH Less thrombocytopenia Bleeding Citrate Lower risk for bleeding Metabolic alkalosis, Hypocalcemia, Special dialysate Prostacycline Reduced bleeding risk Hypotension Poor efficacy Saline flushes No bleeding risk

Dose heparin for CRRT aPTT (seconds) Bolus dose Rate change Repeat aPTT < 40 1,000 U +200 U/hr In 6 hrs 40.1-45.0 Nothing +100 U/hr In 4 hrs 45.1-55.0 No change 55.1-65.0 Stop 1/2 hr and -100 U/hr >65.0 Stop 1 hr and -200 U/hr : Heparin solution is made by mixing 1 ml of 10,000 U/ml of heparin in 19 ml of normal saline for a heparin concentration of 500U/ml. : Initial bolus is 25 U/kg followed by an infusion of 5U/kg/hr. : The goal of treatment is to maintain systemic prefilter aPTT (45 -55 seconds, 1.5 times control)

Common complications for citrate Derangement Cause and signs Adjustment Metabolic acidosis Insufficient removal of metabolic acids Anion gap increases Loss of buffer substrate is higher than delivery Citrate metabolism decreases ( decreases, total Ca/iCa increase [more than 2.1-2.5], and anion gap Increases) Increase CRRT dose (filtrate or dialysate flow) to 35 ml/kg per hr Increase bicarbonate replacement or Increase bicarbonate dialysate flow or give additional bicarbonate or increase citrate flow (cave accumulation) Decrease citrate delivery or stop Increase dialysate or filtrate flow, Increase bicarbonate replacement or increase bicarbonate dialysate flow Metabolic alkalosis Delivery of buffer substrate is higher than loss Decrease loss of buffer due to a decline in filtrate flow Decrease bicarbonate replacement or decrease bicarbonate dialysate flow or stop additional bicarbonate iv or decrease citrate flow (cave accumulation) Change filter Increase filtrate flow Hypocalcemia Loss of calcium is higher than delivery ( decreases and total Ca/iCa is normal) Citrate metabolism decrease ( metabolism acidosis , total ca/iCa increase, and anion gap increases) Increase iv calcium dose decrease or stop citrate delivery increase dialysate or filtrate flow increase bicarbonate replacement or increase bicarbonate dialysate flow Hypercalcemia Delivery of calcium is higher than loss Decrease iv calcium dose Hypernatremia Delivery of sodium is higher than loss Decreased loss of sodium due to a decline in filtrate flow Recalculate default settings Protocol violation Decrease sodium replacement Decrease dialysate sodium content Decrease trisodium citrate flow Hyponatremia Loss of sodium is higher than delivery Increase sodium replacement Increase dialysate sodium content Increase trisodium citrate flow

EXAMPLE : Rt internal jugular catheter : CVVH order BFR 120-150 cc/min, RF (pre-dilution 1,500 cc/hr) Na+, K+, Cl-, HCO3-, Ca2+, UF -100 cc/hr (2,400 cc/day) blood sugar q 6-12 hrs : Dialysate solution 0.45% 900 cc, BUN, Cr, Mg2+, PO43-CBC, , PT/PTT q 24 hrs 3%NaCl 50 cc , 7.5%HCO3 50 cc KCl 3 mEq/L : 10% Calcium gluconate 180 cc/day : 50% Magnesium sulphate 2 cc iv

Common complications in CRRT Vascular access Bleeding Thrombosis Hematoma Aneurysm formation Hemothorax Pneumothorax Pericardial tamponade Arrthymias Air embolism Infection Extracorporeal circuit Reduced filter life Reduced dialysis dose Hypothermia Bioincompatibility Immunologic activation Anaphylaxis Hematologic complications Need for anticoagulantion Hypocalcemia Metabolic alkalosis Hypernatremia Citrate intoxication Thrombocytopenia Hemolysis Heparin-induced thrombocytopenia Electrolyte disturbances Hypophosphatemia Hypomagnesemia Hypokalemia Hyponatremia Hemodynamic instability Volume management errors Nutritional losses Amino acids & proteins Poor glycemic control Vitamin deficiencies Trace minerals Acid-base disturbances Metabolic acidosis Citrate-induced alkalosis & acidosis Altered drug removal Delayed renal recovery

Thank you Acknowledgements Ratchadapiseksompotch Research Fund for projected budget Nipro Company for dialyzer Nurses and Technicians of Division of Nephrology King Chulalongkorn Hospital Thank you for your attention