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![PHARMACOLOGICAL MEASURES
Unfractionated or low molecular weight heparins
Unfractionated heparin (UFH) [5-30kDa] is the most commonly
used anticoagulant
typical regime involves a 40-70 IU.kg-1 bolus followed by a pre-
filterinfusion at 5-10 IU.kg.-1hr-1
It is the most cost effective anticoagulant and is fully reversible
with protamine.
The APTT should be monitored to avoid excessive anti-
coagulation but there is no evidence that elevating the APTT
prolongs filter life.](https://image.slidesharecdn.com/renalreplacementtherapy-150602065636-lva1-app6891/75/Renal-replacement-therapy-36-2048.jpg)
![Low molecular weight heparins (LMWH) [4.5-6kDa]
They are dependant on renal elimination so in this setting
their dosing needs to be guided by anti-factor Xa levels
(aiming for 0.25-0.35 IU.ml-1
The half life of LMWHs is longer than for UFH (2-6 hrs
versus 1.5-3hrs) and their effect can only be partially
reversed with protamine.
There is not a huge amount of data on the use of LMWH in
CRRT and there is no evidence to suggest that they are
superior to UFH.](https://image.slidesharecdn.com/renalreplacementtherapy-150602065636-lva1-app6891/75/Renal-replacement-therapy-37-2048.jpg)
![Dialysis dose
2. Measurement of urea removed through each dialysis.
% of reduction in urea during single hemodialysis treatment –
Urea reduction ratio
[1-(post dialysis BUN concentration) ] x 100
(pre dialysis BUN concentration)](https://image.slidesharecdn.com/renalreplacementtherapy-150602065636-lva1-app6891/75/Renal-replacement-therapy-46-2048.jpg)
Uploaded byDr Kumar
Renal replacement therapy
Dr. Kumar presented on renal replacement therapy. The key points are: 1. Approximately 5% of critically ill patients with AKI will require RRT, with a mortality rate as high as 60%. 2. RRT options include intermittent HD, continuous therapies like CVVH/CVVHD/CVVHDF, and SLED. 3. The choice of RRT depends on the patient's cardiovascular status, resources available, and whether fluid removal or solute clearance is required. CRRT is preferred for hemodynamically unstable patients.
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Dr. Kumar presents RRT; AKI affects one-third of ICU patients, 5% need RRT, mortality at 60%.
AKI is defined as a rapid reduction in kidney function within 48 hours, identified by serum creatinine increase.
RRT is indicated for AKI with fluid overload, hyperkalemia, severe acidosis, and symptomatic uremia, including severe sepsis.
Main components: dialyzer, tubing, and machines; must maintain dialysate purity, critical for effectiveness.
Haemofiltration and haemodialysis utilize ultra and convection filtration with countercurrent flows for solute exchange.
Comparative overview of techniques: haemodiafiltration and slow continuous ultrafiltration; differing fluid removal rates.
Patients requiring RRT typically have complex issues; comparison of continuous vs. intermittent therapies highlights fluid stability concerns.
Common complications of IHD are systemic hypotension, arrhythmias, and infections.
CRRT offers volume control and can improve cardiac index, suitable for prolonged use in critically ill patients.
SLED combines advantages of IHD and CRRT, with daily treatments and better cardiovascular stability.
Factors for choosing RRT include solute removal goals, cardiovascular status, resource availability, and clinician's experience.
Vascular access methods, with pros and cons of IJV, subclavian, and femoral sites regarding infection and comfort.
Various dialysate solutions for buffering and metabolizing, emphasizing importance and adverse effects of high acetate.
Utilizes a pump-driven system to maintain constant flow rate, critical to CRRT effectiveness.
Anticoagulation is essential in CRRT to prevent clotting; discusses heparins, citrate, and their uses.Filters are key in RRT, with biocompatibility, flux, and adsorption as major properties influencing effectiveness.
Common complications across RRT methods, such as infection, instability, and bleeding risks.
Standards for dialysis adequacy revolve around urea clearance, significant for patient health.
Patient management during hemodialysis, ensuring appropriate fluid balance, anemia levels, and vascular access.
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Renal replacement therapy
- 1. Presentor : Dr.Kumar Moderator:Dr.K.Chaitanya Renal ReplacementTherapy
- 2. Introduction It is estimatedthat a third of patients in the critical care setting have an AKI and approximately 5% will require renal replacement therapy . The hospital mortality in patients with an AKI requiring RRT is as high as 60%. no specific treatments have been shown to reverse the course of AKI, so RRT forms the basis of further management
- 3. Definition Acute kidney injury(AKI), is defined as an abrupt (within 48 hours) reduction in kidney function. The AKI network defines the reduction in kidney function as the presence of any one of the following: 1. An absolute increase in serum creatinine of ≥ 0.3 mg.dl -1(≥ 26.4 mcmol.l-1) 2. A percentage increase in serum creatinine of ≥ 50% (1.5-fold from baseline) 3. A reduction in urine output (< 0.5 ml.kg -1 per hour for more than six hours).
- 4. Indications of RRT Acutekidney injury (AKI)with 1. Fluid overload (refractory to diuretics) 2. Hyperkalemia (K+ > 6.5) 3. Severe metabolic acidosis (pH < 7.1) 4. Rapidly climbing urea/creatinine (or urea > 30mmol.l -1) 5. Symptomatic uraemia: encephalopathy, pericarditis, bleeding, nausea, pruritus 6. Oliguria/anuria
- 5. Contd.. Overdose with adialyzable drug or toxin . drugs are cleared by RRT if they are water-soluble and not highly protein-bound
- 6. contd Severe sepsis patientswith ARF have severe sepsis, multiorgan dysfunction and a major systemic inflammatory response. to remove or adsorb inflammatory mediators which cause organ dysfunction may represent yet another reason for its preferential application
- 7. Dialyzer unit Thebasic components of the dialyzer unit: Dialyzer – cellulose, substituted cellulose, synthetic non cellulose membranes. Dialysis solution – dialysate : water must remain free of Al, Cu, chloramines, bacteria and endotoxin. Tubing for transport of blood and dialysis solution. Machine to power and mechanically monitor the procedure Air monitor Proportioning system Temperature sensor Urea sensror to calculate clearance. The basic components of the dialyzer unit: Dialyzer – cellulose, substituted cellulose, synthetic non cellulose membranes. Dialysis solution – dialysate : water must remain free of Al, Cu, chloramines, bacteria and endotoxin. Tubing for transport of blood and dialysis solution. Machine to power and mechanically monitor the procedure Air monitor Proportioning system Temperature sensor Urea sensror to calculate clearance.
- 9. MECHANISM OF SOLUTEREMOVAL Haemofiltration involves blood being pumped through an extracorporeal system that incorporates a semi- permeable membrane. The hydrostatic pressure that is created on the blood-side of the filter drives plasma water across the filter. This process is referred to as “ULTRAFILTRATION”.
- 10. Molecules that aresmall enough to pass through the membrane (<50,000 Daltons) are dragged across the membrane with the water by the process of CONVECTION. The filtered fluid (ultrafiltrate) is discarded and a replacement fluid is added in an adjustable fashion according to the desired fluid balance.
- 11. Haemodialysis involves blood beingpumped through an extracorporeal system that incorporates a dialyzer. In the dialyzer, blood is separated from a crystalloid solution (dialysate) by a semi-permeable membrane. Solutes move across the membrane along their concentration gradient from one compartment to the other obeying Fick`s laws of diffusion.
- 12. For example, bicarbonatemoves from dialysate to blood whereas urea and potassium move from blood to dialysate. In order to maintain concentration gradients and therefore enhance the efficiency of the system the dialysate flows countercurrent to the flow of blood. When removal of water is required the pressure on the blood-side of the membrane has to be increased forcing water molecules to pass into the dialysate.
- 13. Haemodiafiltration as itsname suggests, is a combination of filtration and dialysis. It has the benefits of both techniques but to a lesser extent than when the individual techniques are used on their own. There is no evidence to suggest that CVVDF has a survival benefit when compared to CVVH but may be a useful way of increasing clearance of small solutes.
- 14. Slow continuous ultrafiltration Itis used when the only requirement is water removal. Effectively, it is CVVH with a low filtration rate. It can remove up to 6 litres of fluid a day but solute removal is minimal.
- 15. Modes of RenalReplacement Techniques Intermittent ContinuousHybrid IHDIHD Intermittent haemodialysis SLEDDSLEDD Sustained (or slow) low efficiency daily dialysis SLEDD-FSLEDD-F Sustained (or slow) low efficiency daily dialysis with filtration CVVHCVVH Continuous veno-venous haemofiltration CVVHDCVVHD Continuous veno-venous haemodialysis CVVHDFCVVHDF Continuous veno-venous haemodiafiltration SCUFSCUF Slow continuous ultrafiltration
- 16. Continuous versus intermittentrenal replacement therapy The typical intensive care patient requiring renal replacement therapy have some of the following characteristics, • they are older • multisystem organ failure consisting of sepsis • cardiac failure • adult respiratory distress syndrome • gastrointestinal bleeding • liver abnormalities.
- 17. They aregenerally hypercatabolic, hypermetabolic and require ventilatory support and large amounts of fluid intake to administer inotropes, medications and nutrition. This volume of fluid is administered in the context of a low urine output and increased lung water. This necessitates the need for fluid removal and when implemented with intermittent HD, large amounts of fluid are removed over a small period of time resulting in haemodynamic instability
- 18. Intermittent haemodialysis Intermittent haemodialysisinvolves dialysing with higher flow rates than CRRT for defined periods of time. A typical regime is 3-5 hours of dialysis 3 times a week. The high flow rates and rapid fall in plasma osmolality mean that it is only suitable for patients who are cardiovascularly stable. It forms the basis of long term RRT for chronic renal failure but is not often used in the critical care setting.
- 19.
- 20. Major complications ofIHD Systemic hypotension Arrhythmia Hypoxaemia Haemorrhage Infection Line-related complications(e.g. pneumothorax) Seizure or dialysis disequilibrium Pyrogen reaction or haemolysis ?Delay in recovery of renal function
- 21. Continous Renal replacementtherapy
- 22. SCUF • High fluxmembranes • Up to 24 hrs per day • Objective VOLUME control • NotNot suitable for solute clearance • Blood flow 50-200 ml/min • UF rate 2-8 ml/min • High flux membranes • Up to 24 hrs per day • Objective VOLUME control • NotNot suitable for solute clearance • Blood flow 50-200 ml/min • UF rate 2-8 ml/min
- 23. CAVVH • Extended durationup to weeks • High flux membranes • Mainly convectiveconvective clearance • UF > volume control amount • Excess UF replacedreplaced • Replacement pre- or post-filter • Blood flow 50-200 ml/min • UF rate 10-60 ml/min • Extended duration up to weeks • High flux membranes • Mainly convectiveconvective clearance • UF > volume control amount • Excess UF replacedreplaced • Replacement pre- or post-filter • Blood flow 50-200 ml/min • UF rate 10-60 ml/min
- 24. CAVVHD • Mid/high fluxmembranes • Extended period up to weeks • DiffusiveDiffusive solute clearance • Countercurrent dialysate • UF for volume control • Blood flow 50-200 ml/min • UF rate 1-8 ml/min • Dialysate flow 15-60 ml/min • Mid/high flux membranes • Extended period up to weeks • DiffusiveDiffusive solute clearance • Countercurrent dialysate • UF for volume control • Blood flow 50-200 ml/min • UF rate 1-8 ml/min • Dialysate flow 15-60 ml/min
- 25. Other Benefits ofCRRT Its ability to reduce energy expenditure by cooling the febrile patient, in the patient with heart failure resistant to diuretics, continuous ultrafiltration can produce a rise in cardiac index,while avoiding a fall in arterial pressure. The haemodynamic improvement is mostlydue to a change in preload which optimises myocardial contractility onthe Starlingcurve
- 26. Sustained low efficiencydialysis aims to combine the logistic and cost advantages of IHD with the relative cardiovascular stability of CRRT. Treatments are intermittent but usually daily and with longer session durations than conventional IHD. Solute and fluid removal are slower than IHD, but faster than CRRT.
- 28. WHICH FORM OFRRT SHOULD WE USE? What we want to remove from the plasma
- 29. 2. The patient`scardiovascular status • CRRT causes less rapid fluid shifts and is the preferred option if there is any degree of cardiovascular instability. 3. The availability of resources • CRRT is more labour intensive and more expensive than IHD • Availability of equipment may dictate the form of RRT. 4. The clinician`s experience • It is wise to use a form of RRT that is familiar to all the staff involved. 5. Other specific clinical considerations • Convective modes of RRT may be beneficial if the patient has septic shock • CRRT can aid feeding regimes by improving fluid management • CRRT may be associated with better cerebral perfusion in patients with an acute brain injury or fulminant hepatic failure.
- 30. Vascular access inHD/CRRT Site Advantages disadvantages IJV Straight access Swings in flow associated with respiration. Subclavian Least association with infection. Most comfortable Swings in flow as above. Subclavian vein stenosis if catheter indwelling for a long time. Risks of pneumothorax Femoral Ease of access Infection rates high.
- 31. Dialysate Fluid Bicarbonatebuffer solutions is used in IHD to replenish serum bicarbonate levels and neutralise metabolic acids that are usually present in patients with renal failure. Acetate buffer solutions present the body with a large acetate load to be metabolised by the skeletal muscle. In critically ill patients the acetate levels rise due to decreased skeletal muscle metabolism. Increased acetate levels have been associated with hypotension and hypoxia due to its negative inotrope effect and vasodilatation Lactate buffer soulutions
- 33. Extra corporeal circuit MostCRRT techniques utilise a pump driven venovenous circuit as this provides a high constant flow rate
- 34. Anticoagulation extracorporeal circuit willactivate coagulation pathways and the premature clotting of a filter is a common problem. Even a small amount of clot formation will reduce filter performance. NON-PHARMACOLOGICAL MEASURES 1. adequate central venous pressure, 2. optimising vascular access 3. adding a proportion of the replacement fluid to the patients blood before it passes through the haemofilter (this is predilution)
- 35. GUIDELINES FOR NO ANTICOAGULATION Thereis a already a degree of coagulopathy INR > 2-2.5 APTT > 60 seconds platelet count < 60 x 10³.mm3 There is a high risk of bleeding The patient is receiving activated protein C.
- 36. PHARMACOLOGICAL MEASURES Unfractionated orlow molecular weight heparins Unfractionated heparin (UFH) [5-30kDa] is the most commonly used anticoagulant typical regime involves a 40-70 IU.kg-1 bolus followed by a pre- filterinfusion at 5-10 IU.kg.-1hr-1 It is the most cost effective anticoagulant and is fully reversible with protamine. The APTT should be monitored to avoid excessive anti- coagulation but there is no evidence that elevating the APTT prolongs filter life.
- 37. Low molecular weightheparins (LMWH) [4.5-6kDa] They are dependant on renal elimination so in this setting their dosing needs to be guided by anti-factor Xa levels (aiming for 0.25-0.35 IU.ml-1 The half life of LMWHs is longer than for UFH (2-6 hrs versus 1.5-3hrs) and their effect can only be partially reversed with protamine. There is not a huge amount of data on the use of LMWH in CRRT and there is no evidence to suggest that they are superior to UFH.
- 38. Prostaglandins Prostaglandins (prostacyclin orprostaglandin E2) inhibit platelet function and can either be used on their own or in combination with heparin they have a synergistic effect. short half life (several minutes) so are administered as an infusion (2.5 – 10 ng/kg/.min). The anticoagulant effect stops within 2 hours of discontinuing the infusion The main side effect is vasodilation which may include a reduction in HPV leading to hypoxemia. they are expensive and so are only used as second line therapy
- 39. Regional citrate anticoagulation Itis an effective therapy especially when there is an increased risk of bleeding. It is alternative to heparin Sodium citrate is infused into the circuit pre-filter which chelates calcium and inhibits clot formation. The calcium citrate complex is freely filtered so a calcium infusion is required post-filter. This form of anticoagulation is limited by the metabolic derangements that it can cause: Hypocalcaemia, hypomagnesaemia , hypernatraemia , metabolic alkalosis (citrate is metabolised to bicarbonate), metabolic acidosis (caused by the citrate especially if the body`s citrate handling is impaired e.g.
- 40. Filters Filters are eithercellulose-based or synthetic. Synthetic filters such as polysulphone and polyamide are more biocompatible and are higher-flux membranes so seem more suitable for CRRT high-flux membranes with a surface area of 0.6– 1.2m2 and a pore size allowing the passage of molecules up to 50,000 Daltons
- 41. Properties Biocompatibility o The degreeto which the membrane will activate the patient`s inflammatory and coagulation pathways. o The greater the biocompatibility of a membrane the less activation it will cause Flux o The permeability of the filter. High flux membranes are hydrophobic and may have more or larger pores allowing more water and solute to move across the membrane.
- 42. Adsorption o The abilityof larger solutes to adhere to the surface of the membrane. o A highly adsorptive membrane offers the potential benefit of adsorbing mid sized molecules including inflammatory mediators but only until it is saturated with them (usually after the first few hours) Thickness o Thinner membranes allow greater movement of solute by diffusion and also favour convective movement Surface area o The surface area of the membrane determines the available area for diffusion and ultrafiltration
- 43. Complications common toIHD, CRRT, and hybrid therapies 1. Complications related to the vascath (including line-related sepsis) 2. Haemodynamic instability 3. Air emboli 4. Platelet consumption 5. Blood loss 6. Electrolyte imbalances 7. Hypothermia 8. Effects of anticoagulation (bleeding or specific side-effects of the anticoagulant used e.g. heparin induced thrombocytopenia).
- 44. Adequacy of Dialysis Precise standards and goals of dialysis adequacy are based on the clearance of urea. The volume of distribution of urea reflects the total body water. Mathematical modeling based on the changing blood concentrations
- 45. Dialysis dose 1. Measuringfractional reduction of BUN with each dialysis. Measured by volume adjusted fractional clearance of urea. K*t ÷ V urea Where K – dialyzer urea clearance t – time on dialysis V – volume of distribution of urea
- 46. Dialysis dose 2. Measurementof urea removed through each dialysis. % of reduction in urea during single hemodialysis treatment – Urea reduction ratio [1-(post dialysis BUN concentration) ] x 100 (pre dialysis BUN concentration)
- 47. Care of patientsreceiving hemodialysis Variable Goals Dialysis dose Urea kinetics model Fluid balance Individualised. Intradialytic weight gain should be less than 5% of IBW Quality Measure endotoxin and bacteria in the dialysate water Anemia Target a Hb of 10-12gms%. Avoid high dose erythropoietin Vascular access Monitoring. To establish AV access rather than indwelling catheters. Bone & Mineral Calcium levels between 8.4-9.5 and a PO4 3.5-5.5mg/dl Blood pressure Optimum targets & strategies not well defined LDL cholesterol <100mg/dl Quality of life indices Support from the medical social worker