appratus for peritoneal dialysis fluids.pptx

Peritoneal Dialysis

1. APPRATUS FOR PERITONEAL DIALYSIS -

2. CONTINUOUS AMBULATORY PERITONEAL DIALYSIS (CAPD)

3. Transfer sets PD solution bag is connected to the patient’s peritoneal catheter by a length of plastic tubing called a “transfer set” or “giving set” 3 major types: 1- straight transfer set 2- the Y transfer set, 3- the double-bag system

4. 1. Straight transfer set. Now rarely used because it is associated with high rates of peritonitis One end connects to the peritoneal catheter and the other end to the dialysis solution bag. All exchanges are performed by making and subsequently breaking the connection between the transfer set and the bag. This connection typically involves a spike or a Luer lock. The empty bag and transfer set are rolled up and stored in a pouch carried on the patient’s body.

5. Dialysis is performed as follows: Dialysis solution is instilled by gravity. The empty bag and transfer set are rolled up and stored in a pouch carried on the patient’s body. Dwell time is typically 4–8 hours. The bag is unrolled and placed on the floor. The dialy sate is drained into the bag. The bag is then discon nected from the transfer set and discarded. A new bag is attached to the transfer set using a spike or Luer lock. 6. Fresh dialysis solution is instilled . Once every several months, the transfer set is changed. Extended-life transfer set tubing allows pa tients to dialyze for 6 months between transfer set changes.

6. 2- The Y set During the exchange, the afferent and efferent limbs of the Y are attached to a bag of fresh PD solution and to a drain bag, respectively. Most Y sets are not connected directly to the catheter but rather to a short (15–24 cm) adapter or extension tubing inserted between the catheter and the stem of the Y set. adapter or extension tubing- avoid risk damage associated with, repeated clamping of the catheter

7. Y-set system using flush-before-fill . A : A small volume of fresh dialysis solution is drained directly into the drainage bag (either before or just after drainage of the abdomen). This act washes away any air or bacteria that may be present in the afferent limb of the Y. B : Fresh solution is introduced through the rinsed transfer set. With the preattached double-bag system, the purpose of the “flush-before-fill” step is solely to flush out any air in the tubing

8. a peritonitis rate significantly lower than that with the straight set due to the flush-before-fill. Bacteria that may be introduced during the connection procedure are washed out of the Y set into the empty drainage bag. Less mechanical stress may be placed on the catheter exit site and tunnel - fewer exit site and tunnel infections.

9. solution bag comes preattached to the afferent limb of the Y, obviating the need for any spike or Luer lock connection. drain bag is similarly preattached to the efferent limb. The only connection the patient needs to make is between the transfer set and the adapter/extension tubing. A flush- beforefill step is still performed, but the purpose is only to flush out residual air and not to prevent peritoneal cavity contamination. 3- double-bag Y-set systems solution bag comes preattached to the afferent limb of the Y, obviating the need for any spike or Luer lock connection. drain bag is similarly preattached to the efferent limb. The only connection the patient needs to make is between the transfer set and the adapter/extension tubing. A flush-before fill step is still performed, but the purpose is only to flush out residual air and not to prevent peritoneal cavity contamination.

10. Luer lock

11. PD SOLutions Wegner, a German investigator, was the first to use peritoneal solutions in animals. Heusser added dextrose to the peritoneal dialysis solution to improve ultrafiltration.

12. An ideal pd solution Have a sustained and predictable solute clearance with minimal absorption of the osmotic agents Provide deficient electrolytes and nutrients if required Correct acid-base problems without interacting with other solutes in the peritoneal dialysis fluid Be free of and inhibit the growth of pyrogens and micro-organisms Be free of toxic metals Be inert to the peritoneum

13. PD solution contains buffer which is the source of bicarbonate for correction of acidosis. It can be acetate, lactate or bicarbonate. Dextrose solution contains lactate as buffer.

14. Physiology and Use - Solute removal with dextrose dialysate occurs by means of diffusion across the peritoneal membrane. In 4 hours dwell, urea is > 90 % equilibrated. Creatinine is > 60 % equilibrated. Ultrafiltration with dextrose dialysate occurs across the ultra small pores, also called the aquaporin 1 channels. Higher the concentration of dextrose, higher is the ultrafiltration. The ultrafiltration coefficient is maximum in the initial hour of dwell. This leads to ‘sodium sieving’ in the initial hours of dialysis .

15. Low GDP Solutions -

16. ICODEXTRIN - Mixture of glucose polymer from corn starch. To large to cross the peritoneal membrane. 20-30% absorbed via lymphatics for an 8-16 hour dwell. Hydrolysed into maltose, maltotriose and maltotetrose . Used in 8-16 hour dwell (long dwell in APD and CAPD).

17. PHARMACODYNAMIC AND PHARMACOKINETIC PROFILE : Oncotic pressure created by icodextrin is relatively constant, and ultrafiltration is sustained throughout a long dwell. Icodextrin elimination from plasma follows a one compartment model with first order kinetics. It occurs both by renal excretion and by dialysis during subsequent exchanges. Circulating alpha amylases hydrolyze icodextrin into glucose polymers such as maltose (DP2), maltotriose (DP3) and maltotetraose ( DP4) The steady-state levels of icodextrin and metabolites are constant for at least two weeks of administration with no evidence for long-term accumulation, on discontinuation, blood icodextrin levels return to baseline values with a similar kinetic profile even after many months of administration.

18. ICODEXTRIN AND PERITONEAL ULTRAFILTERATION -

19. Amylase Interpretation An apparent decrease in serum amylase activity has been reported in multiple studies of icodextrin . Icodextrin is a β- glucose polymer consisting mainly of α1, 4- linkages. Amylase breaks α1, 4- linkages. S puriously low concentrations of serum amylase may be Measured

20. INCREASE IN ALP A small increase in mean serum alkaline phosphatase (ALP) has been reported in some studies of icodextrin . T he percentage increase in intestinal ALP appeared greater than for the bone or liver isoforms. P artial inhibition of ALP clearance due to competition between ALP and icodextrin for hepatocyte asialoglycoprotein receptors. Differences in the carbohydrate composition of the intestinal isoform, which is much more heavily asialoglycated , may account for the greater impact on clearance of this isoform.

21. Hyponatraemia Serum sodium levels decreased early after the initiation of icodextrin , were stable over time, and rapidly returned to baseline values after discontinuation of treatment The greatest mean change from baseline with icodextrin was -3.6 mmol/L. Serum chloride typically followed a similar pattern . The decline in serum sodium and chloride associated with icodextrin therapy is caused mainly by a dilutional effect resulting from blood levels of icodextrin metabolites, particularly maltose and maltotriose .

22. The MIDAS study - A randomised, controlled Multicenter Investigation of Icodextrin in Ambulatory peritoneal dialysis (MIDAS) was undertaken to evaluate the long-term safety and efficacy. Compared daily overnight (8 to 12 hour dwell) use of isosmolar icodextrin (282 mOsmol /kg) with conventional 1.36% (346 mOsmol /kg) and 3.86%(484 mOsmol /kg) glucose exchanges over six months. 219 patients from 11 centres . 106 allocated to receive icodextrin and 103 to remain on glucose. 138 patients completed the six month study. The mean overnight ultrafiltration (UF) in icodextrin group was 3.5 times greater than 1.36% glucose at eight hours and 5.5 times greater at 12 hours. No different from that of 3.86% glucose at 8 hours and at 12 hours.

23. The mean serum maltose increased from a pre-dialysis value of 0.04 g/ liter to a steady state level of 1.20 g/ liter within two weeks and remained stable throughout the study. This was not associated with any adverse clinical effects and the overall CAPD-related symptom score was significantly better for icodextrin group.

24. Newer PD fluids- Designed processes to maintain as normal a pH as possible with the use of multi compartmental bags with some or all of buffer as bicarbonate. The buffer compartment is mixed with the glucose compartment immediately prior to infusion. This allows heat sterilization at an optimal pH that would prevent glucose degradation product generation.

25. Physioneal - A neutral pH PD fluid. The buffer is a combination of lactate and bicarbonate. It is manufactured as a two chamber bag.

26. Chamber A - glucose in concentrations of 1.5%, 2.5% and 4.25% at a pH of 2.1 along with calcium and magnesium salts. C hamber B - the buffer at a ph 9.0 with lactate and bicarbonate buffer in it.

27. All additives are to be added to the chamber A, the acidic glucose compartment. Volume of the chambers is in the ratio of 3:1. At least,1.6 l of a bag should be instilled during each infusion to avoid accidental infusion of only the buffer chamber Despite the efforts the GDP concentration of the fluid is still high at 253 μ mol /l /l.

28. Balance Balance (from Fresenius) is a double chamber bag PD fluid with one glucose and electrolyte chamber and another buffer chamber; both in equal volumes. The buffer is lactate . The pH and GDP content of the fluid are 7.0 and 42 μ mol/l respectively.

29. Bicavera Bicavera (from Fresenius) is the only fluid with only bicarbonate as the buffer solution O ne chamber containing glucose along with calcium and magnesium chloride separate from the other chamber with bicarbonate preventing the precipitation of these salts. The pH after mixing of the fluid in the two chambers is 7.4. With the continued use of glucose as the osmotic agent, GDP persist at a low level of 42 μ mol /l.

30. Gambrosol Trio It is manufactured as a tri-compartmental bag with two smaller compartments of 50 % glucose solution and the third larger compartment with electrolytes sodium, calcium, magnesium, chloride and lactate. Mixing one, two or both the smaller compartments to the larger chamber results in low, medium and high osmolar fluids for intra-peritoneal infusion. The pH of the solution after mixing is 6.3 with low GDP concentrations

31. The BalANZ trial - The single largest trial till date comparing neutral pH, low GDP peritoneal dialysis fluid (Balance) to conventional (stay safe) PD fluid. 2 years follow up. The rate of GFR decline though numerically lower was not statistically different in the intervention compared to the conventional PD fluid group. Time to anuria was longer in the Balance arm Number of peritonitis episodes was significantly lower in the intervention arm

32. Trio trial C ompared biocompatible PD solution ( Gambrosol Trio) to standard PD fluid ( Dianeal ) S howed contrasting results with slower rates of GFR decline but higher peritonitis episodes in the intervention arm. This study used bioimpedance analysis to assess volume status Body fat mass was higher in the biocompatible fluid arm. D/P creatinine ratios were similar between the groups

33. TRIO TRIAL – STUDY DESIGN

34. Resultus - RESIDUAL RENAL FUNCTION- Residual renal function declined by 0.132 and 0.174 mL/ min/1.73 m2/month in the Gambrosol Trio and Dianeal arms, respectively. The difference of 0.042 mL/min/1.73 m2/month was significant at p = 0.001. Rates of decline were lower in the biocompatible group regardless of initial RRF or starting PD modality.

35. Results - URINE OUTPUT- Urine volume declined by 30 and 39 mL/month in the Gambrosol Trio and Dianeal arms, respectively (p = 0.003 ). Oligoanuria was observed less frequently in the biocompatible group (p = 0.001 ). Time to anuria was not calculated as 4 of 9 patients with daily urine volumes under 100 mL produced greater than 100 mL on subsequent collections. Mean furosemide use was similar between groups at baseline (63 [38 – 89] mg/day in Gambrosol Trio and 55 [38 – 73] mg/day in Dianeal groups, p = 0.60). Furosemide use increased during the course of the study to a mean of 87 (79 – 95) mg/day and 98 (91 – 106) mg/day in the Gambrosol Trio and Dianeal arms, respectively (p = 0.036).

36. PERITONITIS RATES Peritonitis rates were significantly higher in the biocompatible group . They were not associated with initial PD prescription or subsequent PD modality changes and did not change the finding of slower RRF decline rates in patients treated with the biocompatible solution . C-reactive protein levels did not differ between groups.

37. In 2016, the Cochrane database published a review of trials comparing neutral pH, low GDP fluid to standard PD fluid and summarized the better preservation of residual renal function, urine volume with greater benefit noted through longer use of the solutions ( i.e , longer than 12 months) and lower infusion pain with moderate to high quality evidence . The international society of peritoneal dialysis (ISPD) in its guidelines on management of cardiovascular risk factors suggested the use of biocompatible neutral pH, low GDP fluids for better preservation of RRF when used for longer than 12 months

38. The loss of amino acids (AAs) and proteins into dialysate is substantial to contribute for the nutritional derangements in patients on peritoneal dialysis. Oreopoulos et al. in 1980 proposed an AAs solution in PD both for nutritional supplementation and as an alternative to glucose as the osmotic agent.

39. Amino Acid Solutions The AA mixtures have an average molecular weight of approximately 100 Daltons. This is lower than that of the glucose. Inspite of this, the absorption rate of AAs is not significantly faster than that of glucose. AAs are electrically charged.

40. Osmotic efficacy A 2% AA solution was compared to a 4.25% glucose solution The two solutions induced equivalent amounts of ultrafiltration, similar amounts of urea, creatinine, and potassium removal. At the end of the exchange, 90% of the administered AAs were absorbed . Ultrafiltration achieved with a 1% AA solution was intermediate between that of 1.5% and 2.5% standard glucose solution .

41. Studies which showed lack of definite benefit with AA solutions Young et al, studied ultrafiltration and D/P ratios of several proteins in an 8 hour dwell time exchange using a 1% AA solution in comparison with 1.5% glucose standard solution. Volumes of dialysate at the end of the exchanges were significantly less after amino acid exchanges. Total protein and prealbumin loss into dialysate increased by about 20%. The increase of the peritoneal permeability for proteins was attributed to an activation of the complement by the AAs or their metabolites to produce C5a. AA dialysis solution 1.1% ( Nutrineal ) contains L-arginine, a substrate for nitricoxide (NO) synthase. NO causes vasodilation in many organs.

42. Despite the contradictory results of studies, in clinical practice 1.1% AAsolutions deliver ultrafiltration and small molecule clearances equivalent to those achieved with1.5 % glucose solutions . The differences in these studies are probably due to the difference in concentration and composition of amino acids in the employed solutions .

43. Nutritional efficacy The longest experience with AA solution was a 3-year, randomised, prospective, c ontrolled study of AA dialysate in malnourished Chinese patients on CAPD Sixty patients were assigned randomly to either replace 1 exchange daily with AA dialysate (n = 30) or to continue with dextrose dialysate (n = 30) Biochemical nutritional parameters including albumin and cholesterol decreased in the dextrose group but remained stable or increased in the AA group. Normalised protein equivalent of nitrogen appearance showed a sustained increase only in the AA group. The nutritional benefit of AAs appeared more prominent in women.

44. It is of utmost importance that intraperitoneal administration of the AAs is accompanied by a simultaneous intake of the calories . While the AAs stimulated protein synthesis, the oral calories were found to induce inhibition of protein degradation, thereby reinforcing the positive effects of the AAs on protein balance .

45. Other Benefits of Amino Acid Solution Plasma cholesterol level and triglyceride level decreased during the use of AA solution.

46. Guidelines They are indicated for use only in malnourished or diabetic patients and/or those with recurrent peritonitis. A 1.1 % AA solution consisting of predominantly essential AAs (required by the patients on dialysis) should be used. Sufficient concurrent alternative caloric intake should be guaranteed .

47. Patients treated with one 1.1% AA exchange usually tolerate it well. Two exchanges should be delivered only to patients with very low protein intake; in these cases, a proportional increase in dialysis dose should be considered. AA solutions induced an increased loss of both macromolecules, such as albumin and IgG , and small molecular weight substances. Due to increased release of prostanoids and proinflammatory cytokines into the peritoneal cavity consistent with an increase in peritoneal blood flow and effective peritoneal surface.

48. Conclusions AA solutions can improve the nutritional state of patients on PD with low dietary protein intake. Administration of intraperitoneal AA solutions should be accompanied by simultaneous intake of food containing sufficient calories. In a subgroup of anorectic patients on PD, dialysates composed of a mixture of AAs and glucose in appropriate proportions can serve as a source of both proteins and calories.

49. In patients on APD, a dialysis solution containing such a mixture as a part of a regular nightly dialysis schedule brings about an acute improvement in the whole body protein metabolism, similar to food. Mixing standard AA and glucose solutions by the cycler can be easily performed in the home situation. Using dialysis solutions with a buffer content of 40mmol/L can preserve acid base homeostasis. 1.1 % AA solutions deliver both ultrafiltration and small molecule clearances equivalent to those achieved with 1.5 % glucose solutions. About 18 g of AAs that is 80% of AAs solution is absorbed in 4 to 6 hours of dwell.

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