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Dr Peter Sherren                              Specialist trainee                Anaesthesia and Intensive CareBringing exc...
Bringing excellence to life
Objectives   RRT Indications   Modes and principles   Dosing   Replacement solutions   Anticoagulation   Special Cir...
 AKI / CKD vs ARF / CRF RIFLE Renal failure - is the cessation  of renal function with or without  changes in urine vol...
Bringing excellence to life
Anaesthesia UK. Acute renal failure.                                Renal replacement therapy on ITUBringing excellence to...
“Renal tubular cell injury after a toxic or ischaemic insult results in  sloughing of tubular debris and cells into the tu...
   Renal:       Symptomatic Uraemia       Nephrogenic Pulmonary Oedema       Severe Hyperkalaemia       Severe metabo...
   Early or late initiation of RRT (UO and Urea)   The answer to whether early initiation of RRT is    beneficial with r...
   Intermittent vs continuous   CRRT is an extracorporeal blood purification therapy intended to substitute for impaired...
   Ultrafiltration - movement of fluid across a pressure gradient,    via hydrostatic forces.   Convection - The movemen...
100,000                                                            }                          •Albumin (55,000 - 60,000)  ...
   Intermittent RRT        HD most commonly        Peritoneal dialysis   CRRT     •   SCUF - Slow Continuous Ultrafilt...
   Method      Peritoneal catheter      Instil 1-2 litres dialysis fluid          under gravity   Dialysis Fluid     ...
   Requires AV shunt or Percutaneous catheter.   Removal of solutes by diffusion (mainly small    sized molecules) via c...
   Advantages                                 to waste        Rapid correction of volume overload        Better solute ...
   Primary therapeutic goal:        Safe management of fluid         removal                                  Blood In ...
Access   Primary therapeutic goal:        Convective solute removal                   Return        Management of intra...
   Advantages        Better at removal of middle sized MW         molecules >500-1000 daltons        Use for Cytokine a...
   Primary therapeutic goal:                                         Access        Solute removal by diffusion and      ...
to waste   Advantages                                                   Blood In        Better clearance of small solute...
   Studies in patients with end stage kidney disease (ESKD) requiring IHD    have led to well defined targets for what co...
   Ronco et al 20003 used this approach (ml/kg/hr) to demonstrate survival    benefits of 35 over 20ml/kg/hr.   Kellum e...
   Cellulose        Low flux        Poor at removing middle MW         molecules        Used in end ESRF.        Caus...
   Synthetic     Polysulphone (PS), Polyamide (PA), Polyacrylonitrile (PAN),      Polymethyl methacrylate (PMMA).     H...
   Adjusted based on pt. clinical need   Help drive convective transport   Administered pre or post filter   Must cont...
Contents                         Lactasol         Hemosol BO                         mmol/L           mmol/L     Sodium  ...
   Patients with Liver dysfunction, profound hypoperfusion and pre-existing Lactic    acidaemia are at risk of lactate in...
       Factors affecting filter life:           Access, Anticoagulation, Pre/Post dilution,            Hyperlipidemia, S...
   Heparin                                  Prostacyclin (PGI2)       Intermittent bolus or continuous           Inhib...
Bringing excellence to life
   Principles      Same equipment as haemofiltration      Larger pores in filter      To remove pathogenic material (I...
   Techniques used for extracorporeal drug removal        Haemodialyis        Haemoperfusion        Continuous haemofi...
Substances for which haemodialysis may be used      Salicylates clearance doubled over UA       (seizures/coma/↓pH/AKI/ab...
   HPF was first used in toxicology in the 1960s for barbiturate poisoning   Since these initial reports HPF has been at...
   Carbamazepine                                                        Theophyllines        Causes significant and pro...
   A common ‘non-renal’ indication for CRRT is in the management of severe sepsis.   It has been shown that many, if not...
Any Questions?Bringing excellence to life
   Initiation of RRT should be started earlier rather than later particularly when -        AKI is unlikely to be revers...
   Dose        No clear evidence on dosing and outcome benefit for all AKI        However 35 ml/kg/h of ultrafiltrate p...
1.   Allen R. Nissenson (1998)Kidney International Vol. 53, Suppl. 66  2.   Gettings LG et al. Outcome in post-traumatic a...
8.    Augustine JJ et al. Randomised controlled trial comparing intermittent with continuous dialysis      in patients wit...
15.   Thomas AN et al. Comparison of bicabonate or lactate buffered haemofiltration fluid; use in critically ill       pat...
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Renal replacement therapy

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Renal replacement therapy

  1. 1. Dr Peter Sherren Specialist trainee Anaesthesia and Intensive CareBringing excellence to life
  2. 2. Bringing excellence to life
  3. 3. Objectives RRT Indications Modes and principles Dosing Replacement solutions Anticoagulation Special CircumstancesBringing excellence to life
  4. 4.  AKI / CKD vs ARF / CRF RIFLE Renal failure - is the cessation of renal function with or without changes in urine volumes.Bringing excellence to life
  5. 5. Bringing excellence to life
  6. 6. Anaesthesia UK. Acute renal failure. Renal replacement therapy on ITUBringing excellence to life
  7. 7. “Renal tubular cell injury after a toxic or ischaemic insult results in sloughing of tubular debris and cells into the tubular lumen with eventual obstruction of tubular flow, increased intra-tubular pressure and back leak of glomerular filtrate out of the tubule 1 and into the interstitium and renal venous blood”Bringing excellence to life
  8. 8.  Renal:  Symptomatic Uraemia  Nephrogenic Pulmonary Oedema  Severe Hyperkalaemia  Severe metabolic acidemia  Relative Urea/Creatinine levels Non Renal:  SIRS/sepsis  Fluid balance  Rhabdomyolsis *  Overdose/Drug accumulation  Renal protection pre/post contrast, CIN  Temperature control  Plasmapheresis/Exchange (immune complexes)  Severe acute liver failure with molecular adsorbent re-circulating system (MARS, PROMETHEUS) as bridge to transplantBringing excellence to life
  9. 9.  Early or late initiation of RRT (UO and Urea) The answer to whether early initiation of RRT is beneficial with regards to survival and/or renal recovery is not clear. Why? 2 Getting et al 1999 . Urea 15.2 vs 33.7 conferred survival benefit. 3 4 Ronco et al 2000 and Saudan et al 2006 both dose/outcome studies suggested an early start. 5 Liu et al 2006 observational PICARD study (Urea 27) suggested an early start 6 Not all agree, Bouman et al 2002 RCT no benefit in early initiation of RRT. CvvHFBringing excellence to life Recommendation?
  10. 10.  Intermittent vs continuous CRRT is an extracorporeal blood purification therapy intended to substitute for impaired renal function over an extended period of time and applied for or aimed at being applied for 24 hours a day. Patients with AKI as part of MODS are less likely to tolerate  Fluid shifts  CVS instabiltiy (hyovolaemia and hypotension)  Secondary renal insult In MODS, CRRT is certainly better tolerated in terms of drop in CVP/CO/SVR/MAP 7-9. Likely benefits in for CRRT in SIRS/SEPSIS & cytokine clearance over IHD10. Many papers advocating the benefit of CRRT in patients with raised ICP 12-13. In terms of survival and renal recovery the benefit of either is still to be demonstrated in all AKI requiring RRT. Recent Cochrane Database review 2007 demonstrated important haemodynamic effects but little survival benefits11.Bringing excellence to lifeSo is there a place for IRRT?
  11. 11.  Ultrafiltration - movement of fluid across a pressure gradient, via hydrostatic forces. Convection - The movement of solutes with a water flow or “Solvent drag” Diffusion - Movement of solute from an area of high concentration to an area of low concentration via osmosis across a semi-permeable membrane Adsorption -  Surface adsorption where the molecules are too large to permeate and migrate through the membrane; however can adhere to the membrane  Bulk adsorption within the whole membrane when molecules can permeate it Bringing excellence to life
  12. 12. 100,000 } •Albumin (55,000 - 60,000) 50,000 “large” 10,000 • Beta 2 Microglobulin (11,800) 2 } 5,000 • Inulin (5,200)molecular weight, daltons 1,000 • Vitamin B12 (1,355) “middle” 500 • Aluminum/Desferoxamine Complex (700) • Glucose (180) } • Uric Acid (168) 100 • Creatinine (113) • Phosphate (80) 50 ••Sodium (35) Urea (60) “small” •• Phosphorus (31) Potassium (23) 10 5 0 Bringing excellence to life
  13. 13.  Intermittent RRT  HD most commonly  Peritoneal dialysis CRRT • SCUF - Slow Continuous Ultrafiltration  Ultrafiltration - fluid removal • CVVHF - Continuous Veno-Venous Hemofiltration  Convection - Small, medium and some large size molecules MW <30000 Daltons • CVVHD - Continuous Veno-Venous Hemodialysis  Diffusion - Small molecules <500 Daltons • CVVHDF - Continuous Veno-Venous Hemodiafiltration  Diffusion and Convection- small and medium sized molecules Niche techniques  Plasmapheresis/exchange  HaemoperfusionBringing excellence to life
  14. 14.  Method  Peritoneal catheter  Instil 1-2 litres dialysis fluid under gravity Dialysis Fluid  Similar composition to ECF  Variable Tonicity  Variable K+ and glucose content Advantages  Technically simple  Safer than haemodialysis if:  high risk of systemic bleeding  circulatory instability  vascular access difficult  Indicated in some cases of pancreatitis Disadvantages  Pain  Bowel perforation  Bleeding  Infection/Peritonitis/SP/SEP  MetabolicBringing excellence to life
  15. 15.  Requires AV shunt or Percutaneous catheter. Removal of solutes by diffusion (mainly small sized molecules) via conc gradient. Access Ultrafiltration, via hydrostatic gradient. Very effectively (1-2L/HR) Return High blood flow rates required (350-400ml/min +) Semi permeable membrane is used for selected diffusion. Dialysate is used to create a concentration gradient across a semi permeable membrane. Need dialysate flow +/- countercurrent. The counter-current flow increases solute removal by S maintaining gradient along filter (flow rate 15- 45ml/min, 1-3L/Hr) No replacement fluid Minimal Adsorption Effluent AKI without sepsis or CVS instability.Bringing excellence to life
  16. 16.  Advantages to waste  Rapid correction of volume overload  Better solute clearance than PD/CRRT Dialysate Out Blood In  Intermittent hence mobility (from patient) Disadvantages  Specialist nurses, water tanks etc  Vascular access complications  Anticoagulation Dialysate In Blood Out  CVS instability  NO medium/large molecule (to patient) clearance. LOW CONC HIGH CONCBringing excellence to life
  17. 17.  Primary therapeutic goal:  Safe management of fluid removal Blood In UF rate ranges up to 2 L/Hr via (from patient) hydrostatic forces. No dialysate Fluid Volume Reduction No replacement fluids Large fluid removal via ultrafiltration Blood Out Minimal solute clearance to waste (to patient) LOW PRESS HIGH PRESSBringing excellence to life
  18. 18. Access Primary therapeutic goal:  Convective solute removal Return  Management of intravascular volume (pressure gradient) Blood Flow rate = 10 - 180 ml/min, newer machines 300ml/min. UF rate ranges 6 - 50 L/24 h (> 500 Replacement ml/h) GFR 10-20%. Replacement solution can help to drive convection Removal of small and medium sized molecules No dialysate EffluentBringing excellence to life
  19. 19.  Advantages  Better at removal of middle sized MW molecules >500-1000 daltons  Use for Cytokine adsorption and CVS instability in intractable septic shock10,16 to waste Blood In  Accurate control of ultrafiltered volume (from patient)Repl.  CAVH self-regulating  CVVH requires no arterial access Solution Disadvantages  Complex equipment  Worse clearance/diffusion of small MW Blood Out solutes. NA/K/Ur/Creat  CAVH blood-pressure dependent  Access site complications (esp CAVH) (to patient) LOW PRESS HIGH PRESSBringing excellence to life
  20. 20.  Primary therapeutic goal: Access  Solute removal by diffusion and convection Return  Management of intravascular Dialysate volume Blood Flow rate = 10 - 180ml/min, again newer machines capable of 300ml/min Combines CVVH and CVVHD therapies UF rate ranges 12 - 24 L/24h (> 500 Replacement ml/h) Dialysate Flow rate = 15 - 45 ml/min (~1 - 3 L/h). Countercurrent flow Uses both dialysate (1 L/h) and replacement fluid (500 ml/h+) EffluentBringing excellence to life
  21. 21. to waste Advantages Blood In  Better clearance of small solutes (from patient) over HF, K/Na/Ur/Creat  Less limited by poor access and Dialysate hypotension Solution Repl.  Benefits in ARF & MOF4 Solution  Small/medium/large molecule removal to a degree Blood Out Disadvantages  Not as efficient adsorption and (to patient) middle molecular clearance  Solute and drug clearance less LOW predictable HIGH PRESS  Fluid balance complicated PRESS  Complicated equipment LOW HIGH CONC  Clotted filter may be disguised CONCBringing excellence to life
  22. 22.  Studies in patients with end stage kidney disease (ESKD) requiring IHD have led to well defined targets for what constitutes adequate clearance17 In AKI the dosing/clearance/filtrations rates are not nearly so clear. IHD fractional clearance Kt/V well used. In post filter dilution CvvHF Ultrafiltration volume acts as a surrogate for clearance in the critically ill16. Ultrafiltration volume in ml/kg/hr represents the filtered fraction of patient’s blood. Remember that HDF incorporates diafiltration plus ultrafiltration to give total filtration. Recent studies have described dose of CRRT in terms of ml/kg/h of ultrafiltrate production.Bringing excellence to life
  23. 23.  Ronco et al 20003 used this approach (ml/kg/hr) to demonstrate survival benefits of 35 over 20ml/kg/hr. Kellum et al 200718 pooled 4 recent dose/outcome to demonstrate very large effect on survival in favour of an augmented dose. Landmark multicentre RCT in America (AKI study19) and Australasia (RENAL study20) showed that a high renal dosing regime in RRT conferred no benefit. The ideal dose for CRRT is not known or universally agreed upon; however 35 ml/kg/h of ultrafiltrate production is recommended as a minimum for CVVH (post-dilution) and CVVHDF16. Maybe room for Short term High volume isovolaemic haemofiltration (STHVH) doses of up to 100ml/kg/min or ~8-9L/Hr exchange for severe SIRS/sepsis 10,18.Bringing excellence to life
  24. 24.  Cellulose  Low flux  Poor at removing middle MW molecules  Used in end ESRF.  Cause more complement and leukocyte activation16  Leukocyte retention in the lungs, renal parenchyma and other organs, thus resulting in further organ damage.  Not desirable in the critically ill patient.Bringing excellence to life
  25. 25.  Synthetic  Polysulphone (PS), Polyamide (PA), Polyacrylonitrile (PAN), Polymethyl methacrylate (PMMA).  High flux membranes.  Flux being a measure of ultrafiltration capacity and based on the membrane ultrafiltration coefficient.  High flux membranes are highly water permeable.  Allowing convective therapy and the removal of middle MW molecules.  Better biocompatibility, less complement/leucocyte activation and end organ disfunction16.Bringing excellence to life
  26. 26.  Adjusted based on pt. clinical need Help drive convective transport Administered pre or post filter Must contain:  Sodium  Calcium (except with citrate)  Base (bicarbonate, lactate or citrate) May contain:  Potassium  Phosphate  MagnesiumBringing excellence to life
  27. 27. Contents Lactasol Hemosol BO mmol/L mmol/L  Sodium 140 140  Potassium 1 0  Calcium 1.63 1.75  Magnesium 0.75 0.5  Chloride 100 109.5  Lactate 45 3  Glucose 10 -  pH 5 – 6.5 7.4  Bicarb - 32Bringing excellence to life
  28. 28.  Patients with Liver dysfunction, profound hypoperfusion and pre-existing Lactic acidaemia are at risk of lactate intolerance. Some studies have suggested better control of acidaemia with bicarbonate solutions14 this has not universal though16 Improved cardiovascular stability have also been reported14 To date though use of either base has not demonstrated any survival or renal outcome benefits14-16 Conflicting views, as always! Bicarbonate in theory has some potential benefits but currently no data to clearly advocate one or the other 16 Indications for bicarbonate buffer16  A rise of lactate of greater or equal to 5 mmol/L (from base-line) associated with a worsening metabolic acidosis suggests lactate-intolerance.  Severe pre-existing lactic acidosis pH <7.2 with associated lactate of ≥ 8 mmol/L.  Severe liver dysfunction.Bringing excellence to life
  29. 29.  Factors affecting filter life:  Access, Anticoagulation, Pre/Post dilution, Hyperlipidemia, Sepsis Pre-Dilution  Increases filter life  Increases convective transport  Reduced solute clearance  Some of delivered replacement fluid lost by hemofiltration  Lower anticoagulation requirements  Higher UF required given loss of replacement fluid through filter Post-Dilution  No solute dilution, improved diffusion and solute clearance  Increased hemoconcentration  Higher delivered dose of hemofiltrationBringing excellence to life
  30. 30.  Heparin  Prostacyclin (PGI2)  Intermittent bolus or continuous  Inhibits platelet aggregation infusion  Reduced risk of haemorrhage  Disadvantages  Disadvantage  Haemorrhage  vasodilation and hypotension  Anti-thrombin III deficiency  Thrombocytopaenia  Citrate  Regional heparinisation  Complexes ionised calcium  Ca infused in efferent limb  Low molecular weight heparin  Citrate metabolised Liver, renal and  Less effect on platelet function skeletal muscle.  Direct Thrombin Inhibitors  Some evidence for prolonged filter life and less bleeding events22.  r-Hirudin  Disadvantages  Argatroban  Low Ca++, Low Mg++  Hypotension and tetany  Acidaemia in renal/hepatic impairment as a result of reduced citrate metabolism.Bringing excellence to life
  31. 31. Bringing excellence to life
  32. 32.  Principles  Same equipment as haemofiltration  Larger pores in filter  To remove pathogenic material (IgG/M, paraproteins etc) in plasma  Replace with equal volume of substitute  HAS, FFP  Often rebound antibody synthesis and may need immunosupression Indications  Multiple Myeloma/Waldenström macroglobulinemia and hyperviscocity syndrome (HVS)  Poisoning  SIRS in conjunction with HF, early days  Acute Guillian-Barre syndrome  TTP and HUS  Goodpastures  Meningococcal sepsisBringing excellence to life
  33. 33.  Techniques used for extracorporeal drug removal  Haemodialyis  Haemoperfusion  Continuous haemofiltration  Continuous haemodiafiltration Factors effecting clearance  Molecular size (<500 daltons desirable)  Steric hindrance  Polarity  Volume of distribution, Water/lipid solubility  Protein binding, in particular in HD  Rate of Endogenous clearance  Rate of redistributionBringing excellence to life
  34. 34. Substances for which haemodialysis may be used  Salicylates clearance doubled over UA (seizures/coma/↓pH/AKI/absolute level/paeds)  Lithium  Alcohols: - ethylene glycol, methanol, ethanol, isopropanol  Theophylline HP better  Metformin  (Bromide)Bringing excellence to life
  35. 35.  HPF was first used in toxicology in the 1960s for barbiturate poisoning Since these initial reports HPF has been attempted in the treatment of a number of other poisonings A standard haemofiltration / haemodialysis pump can be used The only special equipment required is the perfusion column Blood is pumped (150 - 250 mL/min) through a column containing an adsorbent, usually activated charcoal, coated with a biocompatible ultrathin membrane Characteristics of compound removed  Adsorbed by charcoal  Vd and endogenous clearance factors similar to previous  Protein binding, water solubility & molecular size are not such limiting factors as with haemodialysis as blood in direct contact with adsorbent NO prospective controlled studies looking at the effect of HPF on outcome in poisoned patientsBringing excellence to life
  36. 36.  Carbamazepine  Theophyllines  Causes significant and prolonged toxicity  Both acute & chronic theophylline (T1/2 19-32 hrs) poisoning can cause significant  Problem of enterohepatic recirculation morbidity and mortality  Binds activated charcoal  Better clearance than MDAC  MDAC vs HP have similar ↑ clearance  Applications in severe OD with dysrrthmias and seizures  iIeus often limits MDAC/whole bowel irrigation  Reserved for life threatening seizure,  Phenobarbitone cardiotoxicity, impaired gut motility or  Both MDAC and HPF increase phenobarbitone clearance, HP to a deteriorating despite MDAC treatment. greater extent  life-threatening toxicity & deterioration despite full supportive care  Others  TCA, Digoxin, Paraquat, Na valporateBringing excellence to life
  37. 37.  A common ‘non-renal’ indication for CRRT is in the management of severe sepsis. It has been shown that many, if not all of the septic mediators can be removed by CVVHF16. Cytokines (IL 1/6/8, TNF, complement, bradykinins, beta-2 microglobulin). Due to the MW of inflammatory mediators it has been shown that CvvHF is particularly effective in their clearance and adsorption16. Due to high generation rate, studies have concentrated on the use of ‘high dose’ or ‘high volume’ haemofiltration. High volume haemofiltration has also been used as ‘rescue therapy’ for patients with severe septic shock unresponsive to other treatments, with encouraging results for cardiovascular stability/outcomes3,10,21,23,24. Ultrafiltration doses as high as 40-85ml/kg/Hr were shown to improve 28 day mortality in septic shock23,24.Bringing excellence to life
  38. 38. Any Questions?Bringing excellence to life
  39. 39.  Initiation of RRT should be started earlier rather than later particularly when -  AKI is unlikely to be reverse early  Patient had normal renal function prior to insult CRRT  Appears to offers some benefits over IHD but no Grade A evidence.  Generally agreed that it is better tolerated in the critically ill. Modality  No clear benefits for one modality over another when addressing the diverse group that is AKI  However, there are encouraging results for the use of certain modalities in specific subgroups (Septic shock ± AKI, ↑ICP, OD, Rhabdomyolysis, Pulmonary oedema, Solute issues, Immunological conditions etc)  Correct modality for the correct patientBringing excellence to life
  40. 40.  Dose  No clear evidence on dosing and outcome benefit for all AKI  However 35 ml/kg/h of ultrafiltrate production is recommended as a minimum for CVVH (post-dilution) and CVVHDF  Higher rates for Cytokine clearance and adsorption in unresponsive septic shock shows some promise Pre-dilution CRRT reduces solute clearance and an increase of 15% for ultrafiltration rates of 2 L/h and up to 40% for rates of 4.5L/h should be considered. Lactate-based replacement fluids are as effective as bicarbonate-based fluids except in conditions where liver function is compromised but there is little evidence that either kind of fluid has survival advantage. Synthetic membranes for CRRT UFH, LMWH and prostacylin are most commonly used, but Citrate may offer some interest for the future.Bringing excellence to life
  41. 41. 1. Allen R. Nissenson (1998)Kidney International Vol. 53, Suppl. 66 2. Gettings LG et al. Outcome in post-traumatic acute renal failure when continuous therapy is applied early vs late. Intensive Care Med 1999;25(8):805-813 3. Ronco C et al. Effects of different doses on continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000; 356(9223): 26- 30. 4. Saudan P et al. Adding dialysis dose to continuous haemofiltration increases survival in patients with acute renal failure. Kidney Int 2006; 70(9): 1312-1317. 5. Liu KD et al. Timing of initiation of dialysis in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol 2006; 1(5): 915-919. 6. Bouman CS et al. Effects of early high volume continuous veno-venous haemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: prospective , randomised trial. Crit Care Med 2002: 30(10): 2205-2211. 7. Davenport A et al. Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure. Crit Care Med 1993; 21(3): 328-338.Bringing excellence to life
  42. 42. 8. Augustine JJ et al. Randomised controlled trial comparing intermittent with continuous dialysis in patients with ARF. Am J Kidney Dis 2004; 44(6): 1000-1007.9. John S et al. Effects of continuous haemofiltration Vs intermittent haemodialysis on haemodynamics and splanchnic regional perfusion in septic shock patients: A prospective randomised clinical trial. Neprol Dial Transplant 2001; 16(2): 320-32710. Patrick M et al. Prospective evaluation of short-term , high volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock. Crit Care Med 2000. Vol 28(11) 3581-358611. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD00377312. Davenport A et al. Changes in ICP during haemofiltration in oliguric patients with grade IV hepatic encephalopathy. Nephron 1989; 53(2): 142-14613. Ronco C et al. Brain density changes during renal replacement in critically ill patients with acute renal failure: Continuous versus intermitent haemodialysis. J Nephrol 1999; 12(3): 173-178.14. Barenbrock M et al. Effect of Bicarbonate and Lactate buffered replacement fluids on cardiovascular outcome in CvvHF patients. Kidney Int 2000; 58 (4): 1751-1757.Bringing excellence to life
  43. 43. 15. Thomas AN et al. Comparison of bicabonate or lactate buffered haemofiltration fluid; use in critically ill patients. Nephrol Dial Transplant 1997; 12 (6): 1212-1217. 16. Standards and Recommendations for the provision of renal replacement therpy on intensive care units in the UK. Intensive Care Society standards and Safety. 01/2009. 17. http://www.kidney.org/Professionals/kdoqi/ 18. Kellum JA. Renal replacement therapy in critically ill patients with acute renal failure: does a greater dose improve survival? Nature Clin Pract Nephrol 2007; 3(3):128-129. 19. VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 359(1):7-20. 20. The RENAL Replacement Study Investigators. Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients. N Engl J Med 2009; 361 (17): 1627-38. 21. Ratanarat et al. Pulse high-volume haemofiltration for treatment of severe sepsis: effects on hemodynamics and survival. Critical Care 2005, 9:R294-R302 22. Monchi M et al. Citrate vs. heparin for anticoagulation in continuous venovenous haemofiltration: a prospective randomised study. Intensive Care Med 2004; 30(2):260-265. 23. Honore PM et al. Prospective evaluation of short-term, high volume isovolemic haemofiltration on the haemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock. Crit Care Med 2000; 28(11): 3581-3587. 24. Ratanarat R et al. Pulse high-volume haemofiltration in critically ill patients: A new approach to patients with septic shock. Seminar Dial 2006,19(1):69-74.Bringing excellence to life

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