ARF vs CRF CKD is of importance grade 1-4, Will concentrate mainly on AKI RIFLE risk, injury, failure, longterm damage, esrf, more itu orientated. 70%vs 30% oliguric/non oliguric . Non oliguric better outcomes
Not that simple though and not so pigeon holed and often multifactorial but a good start Pre-renal Hypovolaemia (Diuretic Induced) G.I. Losses Renal Artery Stenosis; Thrombus Anaphylaxis Dysrhythmias Myocardial Infarction Cardiac Tamponade Congestive Cardiac Failure Vena Cava Obstruction Hypovolaemic Shock Sepsis/Shock Dehydration Intrinsic as above Tubular, Vascular inflamatory vasculitic/IGE/pulmonary renal/thrombotic, Glomulerular, interstitial nephritis, IAH, hepatorenal Post renal Kidney stones and uteric obstruction, clots, tumours, crystals, atonic/neurogenic bladder
Acute tubular necrosis Severe ischaemia, with inadequate supply of oxygen and nutrients to the tubular epithelial cells Poisons, toxins or medications that destroy the tubular epithelial cells, including:
Very diverse list, and probably not exhaustive. OD HP carbomezapine/barbituates/theophylline/TCA CVVHDF aspirin/Benzodiazipnine/MgSO4/Lithium/ethanol/meth/ethylene/aminoglycoside
WHY? hypoten/SIRS/cytokine/renal rest/ATPase/ prior to irreversible tubular injury Ronco et al prospective rct 425 pts and 2 intensive cares, primary endpoint survival at 15 days! Secondary endpoint is recovery of renal function biochemistry and diuresesis. ARF defined by abnormal urea and uo less then 200ml/12 hrs. 20 35 and 45 ml/kg/hr. Not only recommend 35ml/kg /hr but also early starting seemed to confer a better outcome Liu et al clinical Am journal of nephrology 2006 observational study using a urea of 27 as the demarcation of early vs late showed benefit. However Bouman et al 2002 in the critical care medicine a RCT shoed no benefit again in all comers. Not a homogenous group, not one shoe fits all and use of different modalities may confer different survival and benefits. But certainly in ARF with no hx CKD and an unlikely quick recovery would all suggest early initiation would be wise. No negative outcomes demonstrated. Concurred by the recent recommendation by the ICS jan 2009.
IHD is the high filtrate intermittent dialysis Surivival benefits-Difficult randomising CVS unstable patients to IHD IHD not good for CVS unstable SIRS/SEPSIS and removing cytokines. better in terms of small solute clearance, fluid removal, no need for anticoagulation, freedom from machine
Adsorption Molecules that can be effectively adsorbed include:- B 2 Microglobulin- Cytokines- Coagulation factors- Anaphylatoxins
Medium sized molecules blood components cytokines IL1,6 and 8, TNF, bradykinins, endothelin, complement
Leave 30 mins, Drain under gravity over 20 mins or CAPD overnight SCP Sclerosising peritonitis and SEP Sclerosising encapsulating peritonitis.
Dialysate similar in composition to ECF once again
Patrick et al and ICS 10 Patrick et al 2000 crit care med. Prospective interventional 20 pts with intractacble septic shock looking at CI, ph, NA requirement, ScvO2. Using high ultrafiltration rates 85ml/kg/min!
Saudan et al 2006 kidney international Prospective RCT 371, 256 enrolled. AKI all comer group not just sepsis. 28 and 90 day survival significantly higher in CvvHDF group. Not as efficient as CvvHF for removal of medium and large molecules but better than HD. Saudan et al kidney int journal 2006 prospective 371 patients RCT all comer ARF CvvHF or CvvHDF 28 and 90 day survivals
In contrast to ESKD patients, critically ill patients are not in a metabolic steady state, are frequently catabolic and have labile, and often expanded fluid volumes.
Ronco et al Lancet 2000, 425 pts 2 centres, prospective RCT measuring survival at 15 days and renal recovery. ARF reduced UO and urea escalation. 20/35 and 45 ml/kg/hr. Significant survival benefit but no benefit in recovery of renal function biochemistry and diuresis STHVH in Severe sepsis both with either intractable shock and or renal injury Patrick et all 2000
CvvHDF/HF use synthetic
Dialsylate fluid contains elctrolytes at physiological level. It can be adjusted and is similar in some respects to replacement fluid except separated from patients circulation by semipermeable membrane to allow diffusion and equilibrium to be reached. As opposed to being directly added back to the patients circulating volume.
Remember pre dilution replacement will increase filtration rate 15% at 2L/HR and up to 40% 4L/hr
As a general rule, to prevent extracorporeal circuit clotting, clotting times are maintained at 1 ½ times the baseline. Heparin is most frequently used because it is widely available and the best understood anticoagulant. If heparin is contraindicated , tri-sodium citrate (commonly known as citrate) may be used. Citrate protocols anticoagulate the extracorporeal circuit by chelating (or binding with) calcium in the blood. Citrate anticoagulation is complicated by the fact that calcium chloride must be readministered to the patient to prevent tetany and other hypocalcemic effects. Special attention must be given to patient lab values. Literature has also reported the use of Prostacyclin and Nafamostat. At the 5th International Conference on CRRT in March, 2000, Dr. David Ward stated that “of the currently available regimens, citrate and synthetic heparinoids appear to have the greatest safety profile, in terms of reducing the risk of hemorrhage”. Regardless of the method of anticoagulation chosen, the nurse will administer the medication as ordered and will monitor parameters according to established protocol. The patient will be monitored for indications of bleeding and the CRRT system will be monitored and assessed for signs of clotting. If the CRRT extracorporeal circuit clots, it must be removed and replaced with a new circuit. It is important to maintain the vascular access according to established protocol.
MW <500 Higher the Vd the less available in the plasma for excretion Highly protein bound, less free substance available for excretion HD High rate of endogenous clearance eliminates need for extracorporeal circuit
IHD better and has more evidence but evolving for HDF and better for CVS instability Salicylates HD over HP as both have same clearance but HD clears the metabolic/electrolyte/fluid compenents!
Including -carbamazepine, theophylline, salicylates, meprobomate, phenytoin, sodium valproate, paraquat, thallium, dichlorvos, digoxin, tricyclic antidepressants etc Remember requires anticoagulation and can send patient profoundly hypotensive
Ronco et al Lancet RCT 2000, Honore et al crit care med 2000, Ratanarat et al 2006 crit care med. All mortality as primary outcomes! 40-85ml/kg/Hr is the next step and should be considered but is by no mean normal practice.
Early vs late more important in AKI rather than acute on CKD, but weak evidence So to summarize, let’s quickly compare and contrast the four basic CRRT therapies. SCUF is the most simple therapy, its purpose that of patient excess fluid removal. CVVH adds use of pumped replacement fluids, either pre or post filter, to enhance middle molecule clearance. CVVHD does not use replacement fluids, but incorporates use of pumped dialysate to enhance small molecule clearance. CVVHDF is the therapy that combines the benefits of CVVH and CVVHD with use of both replacement fluids and dialysate to achieve optimal benefits for the ARF patient.
Renal replacement therapy
Dr Peter Sherren Specialist trainee Anaesthesia and Intensive CareBringing excellence to life
Anaesthesia UK. Acute renal failure. Renal replacement therapy on ITUBringing excellence to life
“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
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
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. CvvHFBringing excellence to life Recommendation?
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 lifeSo is there a place for IRRT?
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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