OZONE AND DISINFECTION OF HEMODIALISYS MACHINES

 

 

I - INTRODUCTION

 

 

The ozone use to inhibit growth bacterial and the removal of  biofouling, is an efficient way, in the daily pre-treatment of the water tanks, and  the hydraulic circuit of Units of HEMODIALISYS, as well it is used in many places. There is no specific register of ozone job in monitors of hemodialisys, that for its characteristics it contains circuits that allows bacterial proliferation and development of biofouling. The water that cames to the equipment of hemodialisys does not contain chlorine, the dialysis solution presents nutrients as glucose and leave other minerals, in the dialisate has also organic nutrients  proceeding from the patient, the bicarbonate concentrate is a risk well known for infection and the  leaving calcium and magnesium determines formation of irregularities in the  hydraulic circuit, who permits of lodging,  bacterial proliferation and biofouling. Moreover, it can have hiddeen spaces in the internal hydraulic circuit and periods of water stagnation, between dialysis sessions.

This is the first report published on the Ozone job for the internal disinfection of machines of Hemodialisys, in comparative study with Acid Peracetic. The Ozone besides being an excellent bactericidal and a viruscid  agent, also destroys spoors, endotoxins and biofouling for its high oxidative capacity. Affecting the cytoplasm membrane , enzymatic systems and  nucleic acid, determine lise of bacterial cells, not allowing the immunity development or resistance. Inorganic the mucilaginous material and precipitated that they constitute biofouling are oxidized and eliminated with the ozonized water flow. Also it removes precipitated of calcium and magnesium in the places for where it circulates, in way that, with one exactly product can be gotten disinfection it accomplishes e and the calcium removal from  of monitors of Hemodialisys

The induction of chronic inflammatory reply in patients in Hemodialisys, as much for Lipopolissacarídeos as Exotoxins is individualized assets. Recently fragments of DNA of bacteria they had been detected in dialisate, with proven capacity to induce immune reply. ( 1 ).

 

 

 

II-MATERIALS And METHODS

In 2 Units of Hemodialisys were compared the efficiency of the disinfection of machines of Hemodialisys carried through Acid Peracetic in the Unit and the Ozone in the Unit B, applying itself protocol of counting of heterotrophic bacteria and test of endotoxin. The e was collected a total 40 water samples of the dialisate in the Unit 33 samples in Unit B. The collection was daily, occurring in 2 machines per day in each Unit. The samples had been gotten in aseptic way, from connector Hansen of the machines - before the dialysis solution entering in the capillary after 2 hours of Hemodialisys. All machines were Gambro®, model AK 95, being evaluated 9 machines in the Unit and the 10 in Unit B.The hydraulic tubing of machines, for where it circulates the dialysis solution, the dialisate, water, concentrates acid and bicarbonate, are elaborated with some types of materials compatible with ozone, as: polymers (silica, santropeno, PVC , peek, pex,PP, psu, PVDF, ptfe), metals (stainless steel, titanium, platinum) of carbon, ceramics ,aluminum oxide , glass .The diagrams of the hydraulic circuit of the Units and the B are shown in Figures I and II .

 

BACTERIOLOGICAL EXAMINATIONS

The counting of bacteria heterotrophic were carried through the sowing in way of culture Plate-Count-Agar, Merck®, approved for "Standard Methods of will be the Examination Water and Wastewater ", supplying to the results in UFC/ml (units of ml).The plates had been incubates 36º C, for 48 hours. The measure of the concentration of endotoxins was made through limulus amoebocyte lysate (LAL) test, Pyrosate, Cape Cord ®, with one has limited of detention 0,25 I /ml.

 

DISINFECTION of MACHINES In UNIT

 

disinfection of the machines of Hemodialisys in the Unit it was made with mixture of Acid Peracetic, Acid Ascetic and Hydrogen Peroxide, with one final concentration of 0,05% of Acid Peracetic, after the dilution of 1:35, being carried through daily after the last turn of dialysis, per 28 minutes.

 

DISINFECTION of MACHINES In UNIT B

 

It was carried through with Ozone gotten solely for an ozonizer OZONIC ®, through of effect Corona, for the application of an electric discharge on oxygen super-dry, deriving of atmospheric air. The Ozone generation was given local in the Unit of Hemodialisys B, being the Ozone introduced in the water to be purified by means of an injector, through the effect Venturi, to carry through such dissolution. When the Ozone reached the concentration adjusted in the water of looping (above of 700 mV), surveyed for the Monitor Enatron D.

This disinfection with ozonized water was carried through daily, after the last turn of dialysis.

 

accompaniment OF THE LEVELS OF OZONE

 

1)NA OZONIZED WATER

The accompaniment of the Ozone level dissolved in water (residual Ozone) was made through the Monitorial equipment Enatron D.S. ®, that electrode makes the reading of the Potential of Redox (ORP)e of its sensor ( ). The sensor was installed in looping of water ozonized, before the return stops the tank of storage and a signal, deriving of the electrode, fed the Monitor ORP, that it supplied permanently, in a display of the equipment, the concentration of ozone in mV.

 

2) IN THE DIALYSIS MACHINE

The accompaniment of the ozone concentration in dialysis machine was made through ozonized water sample, collected in the drain of the machine, 15 minutes after the disinfection. The reading was made through the dosage of total Chlorine, for colorimetric, with addition of the reagent DPD (N, N-dietil-p-fenilenodiamina). The chemical test was carried through immediately after the collection of the sample of 5,0 ml, comparing visually the gotten color after the DPD addition, in a comparative scale, with water sample treated, not ozonized. The thus gotten values are multiplied by one constant (0,68) to arrive itself at the final ozone concentration dissolved in water in mg/L ( 2 ).

 

Conversion of values in mg/L for mV

 

Through a graph of Potential of Reduction of Oxygen or Potential of Oxi-reduction, shown in Figure III easily the conversion of values gotten in mg/L is made for mV (3 ).

 

DISINFECTION Of TUBING e TANKS

In The Unit it was made through solution I contend Hypochlorite de Sodium in 1% concentration, applied monthly. In The Unit B it was used Ozone, generated as described above, applied daily after the last turn of dialysis, simultaneously with the disinfection of the machines and four times for week, during 3 hours in automatized, controlled way electronically. In this Unit also was carried through weekly thermal disinfection, through warm water circulation enters 85 º C the 95 º C for the looping one, during 100 minutes, being the heat gotten for steel ®constructed a Albacete heater stainless 316, as well as its 6000 resistances of volts each. The tubing of this unit they are of PEX (reticulate polyethylene) that it possess great resistance for high pressures and temperature (up to 140 ° C).

 

Removing Calcium from  Of the MACHINES of DIALYSIS

In The Unit , the stage of removing calcium was made with Acid solution of Ascetic, in 0,5% concentration. In The Unit B no product was not used additional chemistry for calcium removal.

 

ANALYSIS STATISTICS

It was carried through test U of Mann-Whitney and accurate test of Fischer, with program SPSS- MS, presenting itself the results as counting (percentile) and medium (interquartil amplitude P25-P75), being the considered differences significant with P< 0,05.

 

III-RESULTS

 

I How much clinical intercurrences, had not been registered abnormalities in the patients treated in submitted machines the disinfection with Ozone or Acid Peracetic, attributable to these procedures.

 

II How much To CONCENTRATION OF OZONE in the looping one (origin) and the water ozonized collected in the drain of each machine (destination), had been found the following values average, after 30 measuring in each point, as shown in Table I.

 

 

TABLE I. AVERAGE CONCENTRATION OF OZONE In LOOPING and the MACHINES OF HEMODIALISYS

 

 

Measure direct Conversion ( graph ORP)

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LOOPING (n=30) 1033 mV (1023 -1058 ) 2,25 mg/L

 

MACHINES (n=30 ) 0,350 mg/L (0,136- 0,476 ) 760 mV

 

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III-Quanto to COUNTING OF BACTERIA HETEROTROPHIC , in the Unit (the Ac. Peracetic) medium of 17 colonies observed UFC/ml was, in 40 analyzed samples of dialisate. In Unit B (Ozone) medium of 10 colonies UFC/ml was, in 33 samples, as shown in Table II. Statically was found p=0,045, (p< 0,05), evaluated for test U of Mann-Whitney, being the presented data as medium (interquartil amplitude = P25-P75).

 

IV - How much To positively of the Test of the LAL, stops ENDOTOXIN (value > 0,25 EU/ml), in Unit (Ac. Peracetic) 14 positive tests had been registered, in 40 samples, with a percentage of positively of 35 %. Already in the Unit B (Ozone) 6 samples with Test of the positive LAL had been observed, in 33 samples, with a percentage of 18,0%,como appear in Table II.The analysis statistics of this material, carried through for the accurate test of Fischer, it showed one significance of p=0,123, being the presented data as counting ( percentage).

COMPARISON enters OZONE e ACID PERACETIC IN THE DISINFECTION OF HEMODIALISYS MACHINES

 

 

Ác characteristics. Peracetic Ozone p

n = 40 n = 33

 

 

Endotoxins: LAL [ + ], nº (% ) 14 (35) 6 (18) 0,123()

 

Counting Heterotrophy Bacteria. , U/ml 17 (9-28) 10 (3-26) 0,045(b )

 

 

 

The data are presented as counting (percentile) e medium (interquartil amplitude = P25-P75). () Accurate test of Fischer; (b) Test U of Mann-Whitney.

 

The results comparing the job of Ozone and Acid Peracetic, graphical form, how much endotoxins and counting of heterotrophic bacteria, are represented in graphs I and II.

 

GRAPHICAL I. ENDOTOXINS in DIALISATE of HEMODIALISYS MACHINES USING OZONE and ACID PERACETIC

 

GRAPH II

 

BACTERIOLOGICAL EXAMINATIONS in MACHINES OF HEMODIALISYS USING OZONE e ACID PERACETIC

 

How much the frequency of results, the distribution according to UFC number /ml, after Acid Ozone and Peracetic, is shown in Graph III.

 

V How much the abnormalities techniques in machines of Hemodialisys, had been observed some spots of color brown, in the hydraulic circuit and hoses, visible by rough estimate naked, in the machines where if it used Ozone. Moreover, interference of this was evidenced coloration with some alarms. Such spots had not been observed in the machines disinfected with Acid Peracetic.

This material one proved to be constituted of you leave iron, deriving of the acid concentrate used for preparation of the dialisate. Residual deposits I contend iron suffer oxidation for Ozone and assumes the observed brown coloration.

A chemical analysis of the concentration of iron in the acid concentrate mg/L detected 5,44, while in bicarbonate solution (Bicart ®) this concentration was of 1,2 mg/L.

With the job of a solution I contend metabissulfito, in the hydraulic circuit, with frequency weekly, it was gotten removal of these deposits, not having plus none operational interference with the machines of Hemodialisys.

They had not been observed precipitated blockages or of you leave calcium and magnesium to the long one of hydraulic circuit of the machines of Hemodialisys that had been disinfected with Ozone.

 

 

 

IV QUARREL

 

With this study one demonstrates that Ozone reduces in significant way the number of bacteria heterotrophic in monitors of Hemodialisys, an comparison with Acid Peracetic. counting falls of 17 UFC/ml, after disinfection with Acid Peracetic for 10 UFC/ml with Ozone, p< 0,05. Also the presence endotoxins, evaluated for the tests of the LAL, with a limit of detention of 0,25 UE/ ml, was well lesser in the samples of water deriving of monitors dealt with ozone (18 %), in relation to treated with acid Peracetic (35 %).

Exactly with all conditions favorable to the bacterial proliferation, inherent to a monitor of hemodialisys, with ozone had been gotten resulted, in bacteriological terms, that they satisfy the recommendations of the Association of will be the Medical Advancement Instrument (AAMI) (4) and lines of direction of the EDTA (5) for dialisate of hemodialisys.

The concentration of ozone dissolved in the water, measure in the drain of the monitor of hemodialisys, during its application, varied of 0,136 mg/L the 0,476 mg/L, being enough stops to determine reaction of oxi-reduction capable to exert the bactericidal effect desired.

Besides being more efficient that the regimen of disinfection with Acid Peracetic, the protocol with Ozone it determines considerable reduction in the time of the procedure, being able to be made daily after the last turn of dialysis, in 30 minutes, since Ozone if minutos(2 transforms after into oxygen about 15). does not have risk of residual chemical product to remain in the circuit, nor necessity of cleanness of such residues that it consumes time and great volume of treated water. Beyond of this the final cost of Ozone is well inferior to the one of acid Peracetic, therefore it is generated in the proper unit.

Using Ozone, as much the hydraulic net of the Unit as the monitor of Hemodialisys, also the segment of connection between the net and the monitor, are treated simultaneously. This very vulnerable segment, between the Loop and monitor, in some protocols with chemical agents is not reached, consisting in zone of high risk for development of bacteria e biofouling (6), (7). During the period of comment, the patients whose monitors had been dealt with Ozone, had not presented no abnormality clinic.

The monitors of Hemodialisys they had presented only spots of brown color, decurrently of the oxidation of residues of iron gifts in calcium deposited to the long one of the circuit hydro mechanical engineer.

The presence of biofouling it reduces the efficiency of used chemical agents as normally disinfecting, as Hypochlorite de Sodium and Acid Peracetic, generating a vicious cycle, therefore increase of biofouling intervenes with the destruction of bacteria and endotoxins ( 8). The previous use of physical agents with descamantes properties, as acid ascetic, acid citric or acid oxalic, can facilitate the penetration more deep of the deodorant in the structure of biofouling, thus increasing its effectiveness. Although the adequate and periodic disinfection is the best method to reduce the bacterial proliferation in monitors of Hemodialisys, we make use but of protocols validated for elimination of bacteria, lacking still protocols for prevention and eradication of biofouling (9), (10).

Already ozone, for its properties of oxi-reduction, in adjusted concentration, it also destroys for complete biofouling and the its bacteria, also in studies carried through in removable segments of hydraulic circuits of units of hemodialisys, registering this effective destruction of biofouling for way of electronic microscopy (11), (12).

A highest level of decontamination of the monitor it is recommended currently, exactly in Hemodialisys conventional, for the possibility to occur chronic inflammatory reaction in patients with high levels of endotoxins in the dialisate. However the effective decontamination of monitors of hemodialisys continues being a difficulty operational.

The ozone appears as safe, practical, cheap and highly efficient a method to prevent e to remove bacteria and biofouling of monitors of hemodialisys.

 

 

REFERENCES

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2)      Amato R. , Curtis J . The practical application of ozone in dialysis . Neph News &Issues 16 ( 9 ) :27-29,2002

 

3)      The Method of  O3  Residual Control . In  :Handbook of Chlorination  and Alternative  Disinfectants. 4th  Edition. Geo.Clifford White : 1318-1319.

 

 

4)      Association for the Advancement of Medical Instrumentation . Vol 3 : Hemodialysis systems.ANSI/AAMI RD62-2001. AAMI , Arlington , Va. , 2001

 

5)      European Best Practice Guidelines for Haemodialysis .Water treatment system . Nephrol Dial Transplant  17 [ Supplement 7 ] : 45-62 , 2002

 

6)      Ledebo I. Ultrapure diálisis fluid : Improving  conventional and daily diálisis . Hemodialysis Int 8 ( 2 ) : 159-168 , 2004

 

7)      Marion-Ferey  K. ,Enkiri F. , Pasmore M. et al. : Methods for Biofilm Analysis on Silicone Tubing of Dialysis Machines. Artificial  Organs  20 ( 7 ) :658 , 2003

 

8)      Capelli G. , Tetta C. e Canaud B. : Is  biofilm a cause of silent  chronic inflammation  in haemodialysis patients ? A fascinating working hypothesis . Nephrol Dial Transplant  20 ( 2 ) : 266-270 , 2005

 

9)      Lonneman G. When good water goes bad: how it happens , clinical consequences and possible solutions .Blood Purif 22 : 124-129 , 2004

 

10)  Capelli G. , Sereni L. , Scialoja M. et al. Effects  of biofilm formation on haemodialysis  monitor disinfection . Nephrol Dial Transplant  18: 2105-2111 , 2003

 

11)  Penders C. , Kooman J. , Stobberingh E . et al. Does ultrapure  dialysate prevent the development  of biofilm in dialysis  therapy ? Nephrol Dial Transplant  16: 1522-1524 , 2001

 

12)  Smeets E.,Kooman J. ,van Der Sande F. et al. Prevention  of biofilm formation  in dialysis water treatment  systems .Kidney  Int 63 ( 4 ) : 1574-1576 , 2003