PD solutions.pptx

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1. Peritoneal Dialysis solutions

2. History Wegner (germen scientist) first used peritoneal solutions in animals Various different scientists subsequently evaluated efficacy of treating uremia by instilling fluids into peritoneal cavity Gantar treated uremic woman with PD solution containing saline Heusser used Dextrose to improve ultrafilteration In 1938 Rhoads used lactate to correct acidosis Dan baxter company made first commercial PD solution in 1959

3. Solute and water transport in PD Peritoneum contains mainly small pores (40-50Å), Large pores (150Å), and AQP 1- Small pores and AQP1 play major role in slolute and water transport Transport occur by Diffusion and convection Glucose as an osmotic agent promotes Convection Electrolyte transport occur mainly by ultrafilteration as PD solution contains physiological concenteration of solutes limiting diffusion, except potassium which is removed by diffusion

4. Sodium : Due to initial Free water clearance through AQP1 , Sodium Concentration in PD fluid decreases – Short dwells can cause hypernatremia Calcium : Concentration is Higher than plasma – therefore net diffusion from PD solution to blood. Potassium : As PD solution has nil K – predominant transport is by diffusion Bicarbonate : As PD solution doesn’t have bicarbonate – Diffusion from blood to PD solution – Losses offset by generation of HCO3 from lactate in liver In patients requiring higher UF (increased fluid intake) : - Higher Bicarbonate losses leading to chronic Metabolic acidosis.

5. Ideal solution Sustained and predictable solute clearance with minimal absorption of osmotic agent Provide deficient electrolytes and nutrients if required Correct acid base balance Free of microorganisms and inhibit growth of them Free of toxic metals Inert to peritoneum

6. Constituents Osmotic agents Allow net fluid removal by altering osmotic pressure gradient Dextrose is commonly used Comes in three different concenterations – 1.5, 2.5, 4.25 Not ideal, its absorption can lead to metabolic complications such as hyperinsulinemia, hyperglycemia, hyperlidemia , weight gain Glucose degradation products formation is disadvantage

7. Dianeal PD2

8. Glucose polymer solutions Icodextrin is major glucose polymer used in 7.5 % solution Mainly used as substitute in diabetics who require long dwell and in patients with low ultrafiltration capacity The presence of larger molecules in icodextrin solution compared with glucose based solutions improves the osmotic efficiency across the small pores reduces osmotic gradient dissipation This leads to sustatined UF over 8-12 hrs

9. Less metabolic complications Blood concenteration of maltose , maltotriose and other oligopolysaccarides shown to increase with agents Both icodextrin and maltose can cause false positive glucose results Effect on RRF Exposure to glucose causes peritoneal damage, loss of ultrafiltration capacity and progressive decline in RRF. Icodextrin causes relative preservation of intravascular volume and preservation of RRF

10. Effect on ECFV and TBW Declines on Icodextrin with decreased LV Mass Effect on sodium balance and blood pressure Icodextrin causes fluid transport through Small pores leading to both water and sodium removal Dextrose only solutions causes free water removal through AQP leading to sodium retention Hence There is more BP reduction and sodium removal by Icodextrin Effects on peritoneal membrane Less detrimental effects on mesothelium with preservation of peritoneal membrane due to less GDPs and AGE

11. Amino Acid containing solution PD patients lose significant amounts of protein in dialysate (~ 15 g) Therefore used to improve nutritional status Indicated for use only in malnourished or diabetic patients or with recurrent peritonitis 1.1 % amino acid solution containing essential aminoacids should be used

12. Buffers: Lactate- commonly used but may be associated with inflow pain and excessive absorption can cause encephalopathy Acetate : May cause inflow pain and increased incidence of sclerosing peritonitis Bicarbonate : More physiologic, but not compatible with calcium or magnesium containg solutions

13. Electrolytes Sodium : Usually from 130 – 137 mmol/L As water removal exceeds sodium removal – there is predilection for hypernatremia Therefore low sodium concenteration helpful Calcium Standard solution are having 3.5 mmol/L Ca Net calcium gain can occur Low Calcium PD fluids also available

14. Magnesium Usual concentration 0.5 – 1.5 meq /L Lower concentration used as hypermagnesemia is frequent occurrence and it can cause adynamic bone disease Potassium Potassium is usually nil Zero potassium dialysate maintains serum potassium around 4 meq /L In hypokalemia 1-4 mEq /L of potassium can be added to dialysate

15. Other additives : Insulin : Used in diabetics to offset glucose load Intraperitoneal insulin has similar effects as subcutaneous insulin in management of diabetes in PD patients Heparin Added to prevent formation of fibrin in PD fluid Important during peritonitis episodes Intraperitoneal heparin doesn’t lead to systemic anticoagulation

16. Antibiotics Used to treat peritonitis episodes Absorption through peritoneal membrane is enhanced during episodes of peritonitis

17. Glucose degradation products Generated during heat sterilization process 3- Deoxyglucose , 3,4- dideoxyglucosone-3ene, 5-Hydroxymethylfuraldehyde, formaldehyde and acetaldehyde 3,4 DGE is considered most harmful Causes renal tubular epithelial cell apoptosis Adversely effect peritoneal mesothelial cells, fibroblasts, neutrophils and macrophages

18. Newer peritoneal dialysis solutions High glucose concenteration High glucose degradation products Lactate High osmolality Low pH Nat Rev Nephrol   8,  224–233 (2012)

19. Nat Rev Nephrol   8,  224–233 (2012)

20. Nat Rev Nephrol   8,  224–233 (2012)

21. Benefits Residual renal function Neutral pH and low GDP solutions result in better preservation of RRF Due to reduced systemic absorption of reactive carbonyls from peritoneal cavity which are nephrotoxic Residual urine volume Better preserve residual diuresis Shown in balANZ trial in which intervention group experienced significantly lower frequency of anuria (7% vs 20 %) and longer time of onset of anuria compared to conventional PD group Johnson DW, Brown FG, et al: the balANZ trial. Perit Dial Int. 2012;32(5):497-506

22. Peritoneal ultrafilteration No significantly different ultrafilteration when compared to conventional PD soluttions Inflow pain Caused due to acidic pH of conventional solutions , Neutral pH solutions are beneficial Peritonitis Lower peritonitis rates as shown in balANZ trial With lower hospitalisation duration eve if it occured Johnson DW, Brown FG, et al: the balANZ trial. Perit Dial Int. 2012;32(5):497-506

23. Open label, parallel RCT (Nov 2004 to sep 2010), F/U 24 months Neutral pH , Low GDP dialysate vs Conventional PD Solution Primary Outcome : Slope of renal function decline Secondary outcome : Time to anuria, Fluid volume status, Peritonitis free survival, technique survival, Patient survival and adverse events Renal Function decline : Nonsignificant Slower decline in biocompatible group Time to anuria : Significantly longer in Biocompatible group Fluid status : Similar in both groups

24. Time to first peritonitis : Significantly longer and lower rates in biocompatible group Patient survival : Not statistically significant

25. Conclusion Peritoneal dialysis solutions primarily consists of water, osmotic agents and electrolytes Osmotic agents allow net water removal by altering the osmotic pressure gradient- Dextrose is most commonly used Due to significant adverse effects of Glucose containing solutions , newer pH balanced , Low GDP solutions have been developed Cost factor and availability issue remain with these newer solutions