Peritoneal Dialysis Y Connectors In CAPD Patients : Do Subtle Important Modifications Have Potential Role In Reducing Contamination And Rate Of Infective Peritonitis ?

Continuous Ambulatory Peritoneal Dialysis (CAPD) involves transfer of dialysate into and out of peritoneal cavity several times a day with the help of a permanent catheter and connection system. Connection and disconnections during the exchange lead to entry of various organisms into peritoneal cavity and therefore intraluminal infections account for approxintately one-third to one-half of all episodes of peritonitis. It is essential that innovations in technology of peritoneal dialysis delivery system should aim at protecting critical areas of the connectors from accidental contamination and incorporating effective bacterial flushing techniques. Thus the design of the connectors and )(junction is extremely critical in influencing efficiency of any delivery system. V junction plays a critical role in fluid flow path, especially in terms of convective bacterial removal. Central junction of symmetric V set can induce nonlinear turbulent flow and obstruct the flushing process leading to fibrin blockage. Hence, a variation of Y system, known as asymmetric Y set, was developed with an idea to reduce contamination and rate of peritonitis. Asymmetric Y set essentially has straight transparent line to drain the bag combined with short distance between the Y set and patient line. Various single center and small multicentric studies using twin bag with asymmetric V and advanced connectors have shown significant improvement in peritonitis rates. Further, it is essential to assess these innovations by large well-designed RCTs for their usefulness, cost advantage and impact on quality of life.


Y Connectors In CAPD Patients: Do Subtle Important Modifications Have Potential Role In Reducing Contamination
And Rate Of Infective Peritonitis?
A bstruct : C u nti n uousA mh u lalory Perltoneaj Dlalysis (C AP I» involves tr ansfer or d talysa ec into a nd out ofper itoneal cavil)' scvera t nm cs a d ay with the help ora perma nent ca the ter a nd con nec tion system.Connection and disconnections durin:::.the exc ha nge lead to entry uf'variou s u~a nis ms into peritoneal cavtry a nd t herefore infralu minal infections accou nt fo r a pp roximately on e-third tn on e-h alf of a ll ep isode s of peritonitis.It is esse ntia l th a t innovations in tec hno)ug", ' of pcrttoncal di al)'sis delivery syste m should aim at protccnng cr ltlca l a reas of the connectors from accidenta l conta minatio n a nd tncur porau ng effect ive bacteri al tlusbln g technIqucs.Th us the d {'si ~n of t he cc nnccee rs a nd Y-j unction is extremely c r itical in tnnu enctng efflclency of a ny deliver y syste m.Y junction plays a cr itical role in fluid tluw path , especlatty in te rms of cenvecnve bactcria l rem oval.Ce ntra l jun ction of svmm ctr tc Y set ca n induct.' nuntin ear t ur bule nt flow and obst r uct t he ftushtn g proc('ss lcedtn g to fibrin blockage.Hence, a variat ion of Y system, known as asymmctrfc Y set.was developed with an idea to reduce conta mina tion a nd rate of peritonitis.Asym metrie Y set esse nt ially has st raight tran sparent line to drain the b a ~com him'd with short dlvtan ce between the Y set a nd patient line.Var ious stngte cente r a nd small mu lticentric studies ustn g twin baJ!; with asym met ric Y a nd adva nced connectors ha ve show n slgnfftcant Improveme nt in per itoni tis ra tes.Fu r ther, it is essential to assess these innova tio ns by ta rge wetl-deslg ncd H.CTs for th eir usefuln ess, cost ad van ta ge a nd imp act on quality of life, Keyword...: CArn, asym mcrrtc Y set, CAr l>connection system, peritonitis, Y junction tntroductlon: Co ntinuo us Ambulatory Perito neal Dia lysis (CA PO) has been an important modal ity of treatment for end stage renal d isease (ES RD) since the last three and halfdecades'.It offers advantages ofhemodynamic stability, steady-state chemistries, lowe r cost, and improved quality of life with convenience of home therapy, a flexible schedule, and increased freedom " But peritonitis still remain s a major complication ofCA PD.
CAP O involves transfer ofdialysate into and out of peritoneal cavity several times a day with the help ofa permanent catheter and connection system.The possible routes for transfer of organism into peritonea l cavity can be intraluminal (thro ugh the cathete r), periluminal (around the per itoneal catheter), tran smural (viscera l pe rforatio n or migration of bacteria acro ss the bowel wall), hema togenou s and other endogen ous infections such as the retrograde vag inal route.Out of these , intraluminal infections acco unt for approximately one-third to one-half ofall episodes of peritonitis".Adequate hand hygiene measures prior to bag exchange procedure have major impact on touch contamination levels.M iller et al., in 1997 stud ied the numbers of micro -organi sms entering the d ialysis bag durin g a touch-contamination even t in patients undergoing CAPO, so as to identi fy the level of bacterial contamination associated with touch contact o f a connector set.Ten subjects from eac h o f the PO and control grou ps rolled the art ificial spikes lightly between their fingertips for 5 seconds to simulate a touch-contamination eve nt.Approxi mately 500 or fewer micro-organisms were transferred to the connector device, if'it is accidentally touched by unwashed hands (Unprepared hands).Furthermore, if the hands are wet at the time ofcontact, the number of trans locating organisms were as high as 4500 R • Thus the process of connection and disconnections during the exchange can be an important cause of intra luminal contami nation.This facilitates various organisms to enter into peritoneal cavity leading to peritonitis .In order to minimize this risk, improvements of PO delivery systems have aimed at both protecting critical areas ofthe connectors from accidental coruaminationt-" and incorporating effective bacterial flushing techniq ues to remove existing intraluminal contamination.
Advancement in this field include double-bag, Y disconnect systems and advanced connector systems .The design of the connectors and V-junction are both extreme ly critical to the effective performance ofany delivery system in these respects.
Minimizing exposure of dialysate flow pathway to touch contam ination and mechanisms to eradicate contamination before initiating the infusion of dialysate may reduce the incidence of peritonitis.The reduction in the peritonitis rate itselfis sufficient to justify the use of the new systems because repealed infections reduce the capacity of peritoneum for dialysis in future " .This article reviews specific developments in design ofexchange systems forCAPO, highlights importance of asymmetric Y design connector set and its potential role in reducing risk of contamination and peritonitis.

E volution an d Developm ent of CA PD exchange systems: Trends in connectology
Basic compone nts of CAPO exchange systems include bag containi ng dia lysate, tubing from bag to connector assembly and specialized connectors required to connect these to each other and to patients PO catheter and drain bag.This can be a united with all components together or separate compone nts need to be assembled during exchange procedure .
After initial discovery of ambulatory PO by Popovich", first important technologica l innovation on PO exchange system was replacement of glass bottles by collapsible plastic bags.
In this straight connecting system, the dialysate solution bag and peritoneal catheter was connected using a straight piece of tubing and a "sp ike" or a luer lock device.The empty bag after infusing dialysate was rolled up, which remain attached until the next exchange.Hence, in this system the patient had to continuously carry all the plastic elements on his/her body, and was called as wearable system (Fig I).Also, the initial bag and spike system was recognized to result in high incidence of peritonitis due to touch contamination.To overcome touch contami nation and discomfort associated with carrying the system, Buoncristiani et al and Bazzato et al from Italy, introduced the "Y -set'' concept and the double (or twin) bag concept respective ly').procedure the spent dia lysate was drained into the empty bag.Y tubing was the n flushed with a small volume of fresh d ialysat e. followed by introdu ction of fresh dialysate solution into peritoneal cavi ty.
A number of varia nts of v-ser were the n introduced into the clinical pract ice.The most widely used were the long Y set (Y set with long limbs), and the O-set (name d from the shape it takes when two free lim bs are connecte d to eac h othe r du ring the dwell phase).In both systems the patient can disconnect from the bags betwee n exchanges i.e discon nect systems .
In the early years of development Y or 0 set was filled with disin fecta nt duri ng the dwell time and reused in the next exc hange".
However, this had an inherent risk of accidental introduction of the disinfectant age nt into the peritoneum".To further reduce the incidence ofintralu minal contamination.various alternative approaches such as in-line bacterial filters.UV light or heat had been tried at the points of connection.Efforts we re also made to improve the ergonomics and ease of use of the equi pme nt".

Symmetric Y sets with integrated disconnect system
In the earlie r systems, minimum two connections were needed.one between the Y set and the fresh dialysate container, the other between the Y set and the periton eal catheter or the cathete r exte nsion line.To reduce one connect ion between the Y set and the fresh dialysate and to avo id touch contamination. the concept of integrated disconnect system (I DS ) was introduced.IDS consisted of a twin bag.one pref illed with d ialysate and other empty for co llection ofdra inage fluid from peritoneal cav ity with help ofa Y set.Sterility ofthe IDS "dry side" (drai nage line and bag) was mai ntained solely by the steam sterilization process without need of ethy lene oxide or other age nts like gamma radiation.Also there was no need of any d isinfecta nt fluid for the drainage bag and line to ensure the ir ste rility.

Importance of drain-fiush-filt sequence for the bag exchange procedure
A drain-flush-fill seq uence for the bag exchange procedure is based on identificatio n of a backflow phenomenon taking place dur ing the first seconds of the dra inage phase.Th is bac kflow is a seco ndary flow starting at the Y junctio n of the set and go ing up the line to the fresh solution container.The concept utilizes the simple princ iple of physically removing organisms convectively with the flow of dialysis solution.
During an exchange process the peritoneal dialysate is first Indian Journal of Peritoneal Dialysis drained from the peritoneal cav ity into the empty bag .Before introducing the fresh dialysis sol ution into the perito neal cavity, the Yconnectmg system is first flushed with fresh d ialysis solution and drai ned into the empty dra inage bag.This allows any bacteria to be flushed into the spe nt fluid.Th e fresh fluid is then introduced into the peritoneal cavity and the Y connector is d isconnected from the CA PO cathe ter.Flushing from the fresh sol ution container to the drainage container helps to eliminate any contamination.

Nonlinear. turbulent fiow dynamic s with symmetric Y sets
Integral to the e ffective rem oval of bacte ria by "convective flushing" or "d raining of fluid" is the design of the fluid flow path.The most critica l aspect of the fluid flow path, in terms of convective bacte rial remova l will be the Y j unctio n.One frequently encountered problem with Y set is fibrin blockage of drained bag.This is due to the design of central junction of Y set which can induce non linear turbulent flow and can obstruct the flushing procedure":".This can also increase the probabil ity of spi llage and stas is at the end junction po int ofY set.Th e degree of turbule nce and the num ber of entrapment areas present in any given design wi ll likely reduce the efficiency of drain-flush-fill seq uence concept and bacterial removal.However, stra ight path to drain bag may dec rease chances offibri n blockage.So a varia tio n ofY system, known as asymmetric Y set.was developed with an idea to reduce contamination and rate of peritonitis.

Asymmetric Y Set Disconnect System with Twinbag
This system is an IDS with modifications of standard V-set.It consists of a double bag (twi n bag) having a specific geometry ofY j unction i. imp ro vement in the co nnectology of the asy mmetric Y disconnect system".The ma le luer is recessed withi n the connector shroud, ma king to uch contami nat ion virt ually impossible and a female counterpa rt on the patient connector side is such that when the male and female connectors are mated, the surfaces of both connectors are outside the fluid path (Fig 4).In this system even if patient accidentally touch any of these connectors, the design keep that conta minated area outside the fluid path.Thus it is also plausible to assume that the shorter distance between the Y set and patient side, superior flushing technique along with advanced connectology may play an importa nt role in reducing the chance of infection and incidence of peritonitis.The " Y set" in twin bag system of Baxter has asymmetric configuration, which causes flow of In another type of double-bag system, Stay-Safe (SS; Fresenius Medical Care), two bags are connected to tubin g catheters by means of a special switch disc device, which controls and reg ulates all three phases of exchange: outflow, flush, and inflow.The v-tubing connection is built into the contro l disc that consists of a PIN system; turning the knob in the control disc from position I to 4 will com plete the CA PO exchange cycle.In the Stay-Safe System, the tip of the male luer extends to vel)' near the connector shroud and can be easily touched.In addition.the male luer becomes part of the fluid path when the male and female connectors are mated.Therefore, if the tip of the male luer is contaminated during the connect ion process, it is possible for bacter ia to be introduced into the fluid path and therefore into the peritoneum.The tip ofthe female connecto r by des ign is excluded from the fluid path and is unlikely to contribute to conta minationI• .

Impact of PD exchange system modifications on peritonitis rate.
Buoncristiani et al., of Perugia, Italy introduced the Y or the Perugia system in 1980, which prominently reduced peritonitis rates, but it took a long time to satisfy rest of the wor ld regarding efficacy of this simple modification of the orig inal technique.Now, all nephrologists agree with the functioning each new bag excha nge and the concept of "flush befo re fill" was recognized as the the key to the success ofthe Y -c system'".
With the advent of Twinbag systems with asymmetric Y, the focus is shifting to the convective efficiency of the patient drain to remove organisms from the patient transfer set connector to the drain bag than the earlier used flush before fill method to remove contaminatio n 's . Inside

Y set without disinfectant and effectiveness ofjfushbefore-fill
In a study four d isco nn ect systems were used without disinfectant.58 new pat ients including 19 insul in dependent diabetic patients (33 %) were randomized.Th e peritonitis incidence was sta tistically reduced in this prospective study comparing disconnectable systems and conventional syste ms wit h 1/23 patient-months compared to 1/12 .2pat ient-months (p <0.02).The patien ts with high incidence of peritonitis had I periton itis ep isode per 10 patient-months be fore and I peritonitis episode per 24 patient-mont hs after thei r transfer to the y connection (p < 0.00 1).Co nvent iona l CA PO patients (n=4 3) had one perito nitis episode per 11.7 patient-months".
An in vitro study by Verge r and Luzar ex plai ned that a 100 ml flush with dilays ate is effective in steri lizing lines conta minated with common microorganisms respo nsible for touch contaminatio n related infections with low adhes iveness suc h as S. epidermidis>.However. the flush is only partially Twin bag system with asymmetric Y set vs. other PD exchange systems: Peritonitis rates Although a number of devices are avail able curre ntly.but.among them , use of twin-bag disconnec t systems appear to be associated with the lowest rates of infection.Sim ilar result was observed by Kie rnan and colleagues, in a recent prospective randomized clinical trial in 82 pat ients.authors rep orted significantly lowe r rates of periton itis with a twinbag (U ltra Twin ; Baxter Healthcare, Round Lake, IL) vers us a single -bag (Ultra Y set; Baxter Healt hcare, Round Lake, IL) system":"..lO.ll.lW. Sim ilarly outof680 incident CA PO pat ients from 14 centers in the CANUSA study" , 37 used a twin-bag system and 279 use d standard V-set; the I-yr peritonitis-free rate was 79% with a twin-bag sys tem and 66 % with the standard V-set.
The recent systematic review of 12 randomized controlled tria l by Daly C et al fou nd a significant reduction in the risk of peritonitis on com parison of combined ana lysis of standard Y-set or double bag systems with asymmetric Y set and standard syste ms (8 tria ls.626 patients): RR 0.58.95% Cl 0.49 to 0.68) and peritonitis rate (II tr ials, 10082 patient-months): RR 0 .55,95% CI 0.42 to 0.32).Authors also observed that though use of twin bag systems with asymmetric Y set was associated with fewer episodes of peritonitis when compared to standard Y-systems, but the re was no statistically sig nificant advantage (P = 0.05).In a previo us systematic review by the same author, a significantly lower risk of experienc ing periton itis episodes with double bag systems with asymmetric y set com pared with standard V-systems (odds ratio 0.44, 95% CI 0 .27 to 0.7 1) was repo rted", In another prospective contro lled trial" , 14 7 patients commenci ng CAPO were randoml y assigned to one of three groups: the conventional (n=29).standard the Yset (n=57), and the twin bag systems with asymmetric Y set (n=6 1).T hey were followed up for an average of 11.3 months.The maximum average peritonitis-free interval was seen in twin bag (24.8 months (P < 0.00 1» followed by the Y system (12 .0months) and then co nventiona l group (6 .1 mo nths).Multivariate analysis further revealed CA PO system to be only factor associated with peritoniti s.Peritoniti s-re lated hospitalizati on was seen most in conve ntiona l syste m (5.3±2.0 days/patient/ year ) when compared to Y syste m (2.7 ± 1.0 days/patient/year) and twin bag system ( 1.5±0.9days/patient/year ).There was a 50% reduct ion in peritonitis inc idence with the V-set and a 75% reduction with the twin-bag co nfiguration as compared with standard-bag systems.
The effect of asymmetric Y system on peritonitis incidence and patient morbidity was also eva luated in a comparative, retros pective single -cente r ana lysis ove r a period of 5 yea rs.Introduction of IDS with assymetr ic Y led to improvement in the peritonitis-free period from I: I I patien t-m onths (conve ntional system), to greater than I:50 patient-months (assy met ric -Y system).The rate of hospitalizatio n was a lso decreased by 45% J6.
Anothe r single-cente r random ized study performed in 63 adult patients compared the efficiency and total cost of Fredine Solo (FS.twin-bag) and Basic V (BY.sing le-bag) system s".After a total follow-up 01'631 patient months, cumu lative incidence of peritonitis was I per 14.0 patient months with BY and I per 46.5 patient months with FS (odds ratio, 3.6; 95% CI 1.5 to 8.5; P = 0.004).
Similarly 15 CAP O patients were stud ied using two different types of exc hange systems: a snap-disconnec t Ysct syste m and the Baxter UltraBag syste m with asymmetric Y set.The inc idence of peri tonit is in patients using snap -disconnect V-system was found to be 32 cases in 187 months, or a rate of I case of peritonitis episode every 5.8 months.Switchi ng these patients to the Baxter UltraBag syste m, resulted in highly significant decrease in incidence ofperitonitis to 4 cases in 175 months, or I case every 43.8 months".In another study the peritonitis rate lo r the standard "Y" set (Fredine I and 2 T .M. Use of all the discon nectablc systems is associated with the increased cos t of the supplies.But, it is of little matter of concern when compared to benefits of the Y set: decrease in per itonitis.less hosp italization, dec rease in protein losses , no additive cost ofantibiotics, etc.".Monteon et al 1991-\ found the cost per bag as sim ilar lo r the conventional and Y syste m. but higher forthe twin bag.However, the total costs of treatment (pesos/patient/year) were lower for twin bag (62 ,159 for the conve ntional.70.275 for the Y system, and 54,31-\7 for the twin bag), due to the lower peritonitis incidence, decreased usage of ant ibiotics and fewer hosp italizations.Thus the reduction in the periton itis rate itself is sufficient to justify the use of the new systems on economic grounds .
Better conncctology and subtle important modifications in Y connector systems may also lead to better quality of life.On ly two studies comparing double bag with a standard Y-sct system reported quality of life data.Harris 1996, using a Lickert scale, reported significantly greater "ease of use" and Li 1996.using a e-itcrn q uestionnaire, reported significantly greater " patient acceptability" with the double bag system.However, these instruments of assessme nt still need to be validated in this particular seuing.

Implications f or clinical practice & futu re research ;
Continuous quality initiatives in CAP O excha nge systems can significantly reduce peritonit is rates, thereby reducing cost and need for hospitalization.improving abil ity to maintai n patients on I'D, and enhanc ing patients' quality of life.The studies show a significant benefit ofusing twin bag systems with asymmetri c Y set.Ilo..... ever.measures like aggressive patient traini ng and period ic retra ining every six months.using equipment from a single reliable PO manufact urer for all patients and other organized initiatives towa rds preve nting infections can add to peritonitis reduction considerably'.
Though many single centre and mu lticentric studies have shown the benefit of using twin bag with asymmetric Y and advanced connectors, for CAPO, it is essential that innovations in technology designed to reduce pe riton it is rates sho uld

Figure 1 :
Figure 1: The Wea r abl e Straight Connecting System with Rolled up Bag Figu re 3: Asymmetric Y set Disconnect System

Figure 4 :
Figure 4: Connectology of Asymmetric Y set Disconn ect System effective whe n S. aureus and Pseudomonas species were present .In anot her prospect ive controlled study.Verger et al compared the efficacy of CA PO Y-li nes without disi nfectant and standard CA PO syste ms with and without d isinfectant" .It was concluded that V-set CAPO systems are significantly more effective than standard CA PO in preventing peritonitis.eve n Indi an Jo urnal o f Perito neal Dialy si s when an antiseptic is use d with the latter.Enhancing efficacy of the flush-befo re-f i l l tec hnique will require larger volumes being used at the flushing time.T hus it wo uld be necessary to increase the initial volu me of the bag to avoid a decrease in the inflow vo lume.
be assessed by well-des igned RCTs.Th e do uble bag with I I .asy m met ric Y set should be further tested in large scale tria ls in Ind ia to assess the significance of rcducing periton itis rates in terms ofcost advantage and quality of life.Trials should be designed in a way 10 clearly identify the beneficial intervention or ad verse effects amongst the various adv ances in C APD 2 I .exchange systems.Th is may help in guid ing the PD therapy and further improving patient outco mes.
the Patient C oonernon to I episode per 68 pt months after 10 years of usage20.In a two year prospective randomized trial comparing symmetric Y connect ion versus conventional techniq ue of spike systems in prevention of peritonitis episodes, new patients (n=27) with Y connection had I episode every 23 patient-months as compared to 12.2 pat ient-months (p<O.02) in those on the conventi onal syste m (0=28)21.Y set with disinfectant -Peritonitis ratesAnothe r study by Cantaluppi et al.," revealed that inc idence of peritonit is rate dec reased from one episo de every 52.5 patient-months to one episode every 76 patie nt-months, when the d iabe tics were excluded.Similar findings have also been repo rted by Bazzato" .
centers comb ined was 22.9 patient-mont hs/ep isode for AN DY-Disc and 35.0 patient-months/episode for UltraBag (1' =0.033 ).The risk of per itonitis was 53% greate r for AN DY-Disc compared to UltraBag w .
A multicenter (6 ce nters), o pen-label .pa rallel-group, randomized tria l was cond ucted over a period of 12 months (Ap ril 2002 to May 2003) with 270 new or existing CA PO patients using a single-bag system, 2 12 patients (AN DY-Disc 102, UltraBag 110) completed the trial.The ove rall peritonitis II rate for all