European Urology 48 (2005)

Transcription

1 European Urology European Urology 48 (2005) Hydrophilic-Coated Catheters for Intermittent Catheterisation Reduce Urethral MicroTrauma: A Prospective, Randomised, Participant-Blinded, Crossover Study of Three DifferentTypes of Catheters J. Stensballe a, *, D. Looms b, P.N. Nielsen b, M. Tvede c a Department of Anaesthesia and Operating Theatre Services, 4231, Centre of Head and Orthopaedics, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark b Clinical Documentation, Continence Care Division, Coloplast A/S, Denmark c Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Denmark Accepted 15 July 2005 Available online 2 August 2005 Abstract Objective: To compare two hydrophilic-coated (SpeediCath 1 and LoFric 1 ) and one uncoated gel-lubricated catheter (InCare 1 Advance Plus) concerning withdrawal friction force and urethral micro trauma. Methods: 49 healthy male volunteers participated in this prospective, randomised, blinded, crossover study of three different bladder catheters. The withdrawal friction force was measured, and urine analysis of blood, nitrite and leucocytes, microbiological analysis of urine cultures and subjective evaluation of the catheters were performed. Results: 40 participants completed the study and were included in the analysis. SpeediCath 1 exerted a significantly lower mean withdrawal friction force and work than the gel-lubricated uncoated catheter, whereas LoFric 1 exerted a significantly higher mean friction force than both of the other catheters. The hydrophilic catheters caused less microscopic haematuria and less pain than the gel-lubricated uncoated catheter. Furthermore, 93% of the participants preferred the hydrophilic catheters. Conclusion: Hydrophilic-coated catheters perform better than uncoated catheters with regard to haematuria and preference. SpeediCath 1, but not LoFric 1, exerts less withdrawal friction force than InCare 1 Advance Plus. # 2005 Elsevier B.V. All rights reserved. Keywords: Intermittent catheterisation; Hydrophilic-coated catheter; Friction force; Haematuria; Urethral trauma 1. Introduction Since Lapides et al. [1] introduced clean intermittent catheterisation (CIC) as a bladder management method, use of the technique has resulted in improved kidney and upper urinary tract status, lessening of vesicoureteral reflux and amelioration of continence in patients suffering from neurogenic bladder dysfunction [2]. These beneficial effects are associated with the technique as such and are not influenced by the type of catheter used. * Corresponding author. Tel ; Fax: address: jakob.stensballe@rh.hosp.dk (J. Stensballe). However, catheter surface properties may influence other aspects of CIC, such as urethral complications, urinary tract infections as well as patient satisfaction and preference. Urethral complications associated with repeated catheterisation range from urethral mucosa irritation over urethral lesions, to strictures and false passages [3,4]. Hydrophilic-coated catheters are characterised by having a layer of polymer coating that is bound to the catheter surface. The polymer absorbs and binds water to the catheter, resulting in a thick, smooth and slippery surface. The coating layer remains intact upon introduction into the urethra and ensures lubrication of the urethra in its entire length. Apart from the fact that they /$ see front matter # 2005 Elsevier B.V. All rights reserved. doi: /j.eururo

2 J. Stensballe et al. / European Urology 48 (2005) lead to a better patient satisfaction [5,6], the hydrophilic-coated catheters are assumed to reduce the risk of urethral damage by decreasing the friction exerted when the catheter is inserted and withdrawn. However, it is difficult to directly demonstrate reduced urethral trauma in a clinical setting. Several indirect approaches have been used to assess urethral trauma caused by intermittent catheterisation. One of these is measuring catheter withdrawal friction force. If a catheter exerts a high level of friction on the urethral wall, it is assumed that damage to the epithelium will also be increased with long-term use. Another way of assessing the degree of urethral damage is to analyse the abrasion of epithelial cells by performing urethral cytology [4], or to count epithelial cells on the surface of used catheters [7,8]. Furthermore, haematuria is often used as a parameter for evaluating the degree of urethral trauma. Previous studies have shown that the degree of urethral inflammatory response is decreased in spinal cord-injured patients using hydrophilic-coated catheters for CIC compared to patients using uncoated polyvinyl chloride catheters [4]. In rabbits, it has been shown that differences in hydrophilic catheter coating can have a significant effect on the withdrawal friction and epithelial cell damage [9]. Furthermore, in a clinical study comparing two hydrophilic-coated catheters, the level of withdrawal friction was suggested to be linked to the osmolality of the outer layer of the catheter [10]. There have been no reported clinical trials comparing hydrophilic-coated and uncoated catheters with regard to withdrawal friction. This study was designed to test the hypothesis that hydrophilic-coated catheters exert less urethral friction and, hence, cause less urethral micro trauma. 2. Methods and Materials The objective of the study was to compare two hydrophiliccoated and one uncoated, lubricated catheter with regard to withdrawal friction force and urethral micro trauma. The primary endpoint was the friction force when the catheter is withdrawn, measured at 10 mm/s with a LRX tension testing system using a 10 N loadcell (Lloyd Instruments Ltd., UK) as shown in Fig. 1. The secondary endpoints were: (1) incidence of haematuria, leucocytes and nitrite measured by urine dipsticks, (2) incidence of bacteriuria measured by urine culture and sensitivity test and (3) subjective evaluation of the catheters. The study was carried out by two specially trained research nurses with experience of more than 1000 intermittent catheterisations, supervised by a medical doctor. Study participants were recruited among healthy volunteers following advertisements on two Danish university bulletin boards and in a Danish online magazine for medical students. Volunteers included in the study had to be at least 18 years old, male, with negative urine dipstick Fig. 1. Standardised measurement of withdrawal friction force. The participant was seated in a chair with a fixed angle between back and seat of A curtain obstructed the participant s view of the entire catheterisation process. The research nurse inserted the catheter in its full length, followed by urine drainage into a bag connected to the catheter. Immediately after disconnection of the urine bag, a conic stopper was firmly inserted into the catheter connector. A string attached to the stopper was connected to the loadcell via a guiding wheel to ensure standardised catheter withdrawal. Furthermore, a chute was placed between the legs of the participants at a 458 angle with the seat. Penis and catheter rested on the chute during the entire catheter withdrawal process. Once everything was in place, the measurements were initiated by pressing a button. Thus, the actual data collection was performed automatically by the standard software controlling the tension-testing system. (blood, leucocytes and nitrite) at the first visit and had to have given their verbal and signed, informed consent to participate. Subjects with experience of recurrent urinary tract infections, known congenital urogenital abnormalities or known urethral strictures were excluded from participation. The study took place at Coloplast A/S Continence Care Division. The catheters tested were: Conveen SpeediCath 1 (Coloplast A/ S, Denmark) with a hydrophilic ready-to-use coating, InCare 1 Advance Plus (Hollister Inc., U.S.A.) an uncoated silicone/pvc catheter with gel, and LoFric 1 (AstraTech, Sweden) with a hydrophilic coating where water is added 30 s prior to use. All catheters used were for single use, size CH12, CE-marked and sold on the European market. On the first of the three visits, the participants were randomised to the sequence of catheter type. In a crossover design, each participant was catheterised twice on the same day with the same catheter, with at least two days between test visits. Only participants who were catheterised twice with all three catheter types were included in the analysis. In a pilot study, an average force difference of 0.07 Newton (N) was found between SpeediCath 1 and LoFric 1 with a standard deviation of N (Coloplast, Clinical Investigation Report DK018CC). A sample size of 35 should have 90% power to detect a difference in means of 0.07 N, assuming a standard deviation of N, using a paired t-test with a 0.05 two-sided significance level. Similar calculations showed that a sample size of 10 was sufficient to detect a difference between SpeediCath 1 and the Hollister catheter. In order to detect a difference between Speedi- Cath 1 and both alternative products, a sample size of 35 was

3 980 J. Stensballe et al. / European Urology 48 (2005) chosen. To compensate for non-evaluable patients, it was planned to include approximately 50 participants. The randomisation list was produced electronically by computer using software Medstat version 2.1. Consecutively numbered randomisation envelopes were delivered to the research nurses. On all three test day s participants were blinded with a curtain so that they could not see which catheter brand they were testing. The research nurses were not blinded, as it was impossible to conceal the type of catheter. The microbiologist analysing the urine samples was blinded. Average friction force and average work needed for withdrawal were analysed using a two-sided ANOVA test (with catheter and participant as factors). The Bonferroni test was used subsequently for pair-wise comparison. The level of haematuria and the subjective evaluation by the participants of insertion and withdrawal of catheters were analysed using the Friedman test with subsequent Wilcoxon test for pair-wise comparison. Assessments of discomfort during micturition following catheterisation were analysed using the Cochran s Q test with subsequent McNemar test for pair-wise comparison. Data were entered twice into a data management system (Medloc, SAS Institute A/S, Denmark). The statistical analysis was performed using SAS version 8.2 with a 5% level of significance. 3. Results 3.1. Participants A total of 50 men volunteered to participate in the study. Forty-nine participants were included in the study, one did not show up. Of the 49 participants, nine stopped before completing the study as shown in Table 1. Thus, 40 participants completed the study and were included in the analyses. Participants were recruited from January 2005 to March The mean age was 24 years (range 18 42). None of the participants received any concurrent medication Withdrawal friction force The primary endpoint of the study was to compare the withdrawal friction force for the three catheters tested. The average withdrawal friction force is shown in Table 2. The difference between the products was statistically significant (p < , ANOVA analysis). Table 2 Average withdrawal friction force for the three catheter brands Catheter Brand n Average Force (Newton) Mean SpeediCath InCare 1 Advance Plus LoFric Pair-wise comparison of the products was also significant (p < 0.05, Bonferroni test) with SpeediCath 1 exerting a lower mean friction force on withdrawal than both InCare 1 Advance Plus and LoFric 1, whereas InCare 1 Advance Plus exerted a lower force than LoFric 1. The difference between the catheters with regard to average work needed for withdrawal of the catheters (Table 3) was also statistically significant (p < , ANOVA analysis). Pair-wise comparison of the catheters showed a statistically significant difference (p < 0.05, Bonferroni test) in favour of SpeediCath 1 when compared to InCare 1 Advance Plus and LoFric 1, and a significant difference in favour of InCare 1 Advance Plus when compared to LoFric Urine analyses One of the secondary endpoints with regard to safety was the incidence of haematuria, leucocytes and nitrite measured by using urine dipsticks. The results of the analyses performed after the catheterisations with regard to haematuria are shown in Table 4. The dif- Table 3 Average work needed for withdrawal of the three catheter brands, calculated as the area under the curve of the friction force measured versus length of withdrawal Catheter Brand n Average Work (Joule) Mean SpeediCath InCare 1 Advance Plus LoFric SD SD Table 1 Number of participants included, discontinued and included in analysis Participants included 49 Participants discontinued 9 Not possible to catheterise 4 a Lack of time due to work/study 2 Level of discomfort too high 3 b Participants included in analysis 40 a LoFric 1 n = 2, InCare 1 Advance Plus n =2. b InCare 1 Advance Plus n = 2, SpeediCath 1 n =1. n Table 4 Dipstick analysis of blood content in urine from first normal micturition after two catheterisations performed with the catheter Erythrocytes/mL SpeediCath 1 InCare 1 Advance Plus LoFric 1 n % n % n % Negative /+/ / / /

4 J. Stensballe et al. / European Urology 48 (2005) Table 5 Subjective evaluation by the patient of sensation at insertion of the catheter All in all how do you feel the catheter during insertion? SpeediCath 1 InCare 1 Advance Plus LoFric 1 n % n % n % I could not feel it I could feel it, but it was not painful I could feel it and there was some pain I could feel it and it was painful Total ference between the products was statistically significant (p = , Friedman test), with less haematuria in the samples obtained following catheterisation with the hydrophilic-coated catheters. Pair-wise comparison of LoFric 1 and the gel-lubricated uncoated catheter showed a significant difference in favour of LoFric 1 (p = , Wilcoxon test). The urine samples taken before the catheterisations were also found to be negative for erythrocytes. All urine samples before and after the catheterisations were negative with regard to nitrite and leucocytes. Bacteriuria measured by urine culture and sensitivity test was found in six participants, who were included in the analyses. Of these, only three had significant bacteriuria with bacterial counts of 10 3 CFU/mL or more, and only two of these were symptomatic and received antibiotic treatment. None of the remaining participants with positive urine cultures had clinical symptoms. The incidence of bacteriuria could not be associated with the use of a specific catheter. Furthermore the exclusion of these six participants from the analysis did not affect the results of the primary endpoint (withdrawal friction force) Subjective catheter evaluation The result of the subjective assessment of sensation during insertion of the catheter is shown in Table 5. The difference between the catheters was statistically significant (p < , Friedman test). Pair-wise comparison of the catheters using the Wilcoxon test was also significantly in favour of SpeediCath 1 when compared to InCare 1 Advance Plus (p < ) and LoFric 1 (p = 0.049) as well as in favour of LoFric 1 when compared to InCare 1 Advance Plus (p = ). Similarly, there was a statistically significant difference between the three catheters with regard to the subjective assessment of sensation during withdrawal of the catheter (p = , Friedman test). However, the pair-wise comparison was only significantly in favour of SpeediCath 1 over InCare 1 Advance Plus (p = , Wilcoxon test). Table 6 Participants preference as to catheter type Catheter brand n % SpeediCath InCare 1 Advance Plus 1 2 LoFric No preference 2 5 When the participants were asked whether or not they had experienced any discomfort such as pain or stinging during micturition after catheterisation, 70%, 45% and 68% answered no after using SpeediCath 1,InCare 1 Advance Plus and LoFric 1, respectively. The difference between the catheters was statistically significant (p = , Cochran s Q test). However, there was no significant difference in the pair-wise comparison of the products with regard to this parameter (p = SpeediCath 1 /InCare 1, p = 1 SpeediCath 1 /LoFric 1, p = LoFric 1 /InCare 1 ; McNemar test). The results of the assessment of catheter preference are shown in Table 6. Ninety-three per cent of the participants preferred the hydrophilic-coated catheters SpeediCath 1 and LoFric Adverse events Two test participants experienced adverse events. One test participant experienced eczema on the penis and a urinary tract infection. The other test participant experienced a urinary tract infection. All three adverse events were considered possibly related to the use of catheters. No serious adverse events were reported in this study. 4. Discussion This study was designed to test the hypothesis that hydrophilic-coated catheters exert less urethral friction and hence cause less urethral micro trauma measured as withdrawal friction force and haematuria. The results show that the withdrawal friction force was

5 982 J. Stensballe et al. / European Urology 48 (2005) significantly lower for the hydrophilic-coated Speedi- Cath 1 catheter compared to the other two catheters tested. Surprisingly, however, the other hydrophiliccoated catheter, LoFric 1, was found to exert a significantly higher withdrawal friction force than the gellubricated uncoated catheter. Thus, there seems to be no basis for accepting the hypothesis that hydrophiliccoated catheters, in general, exert lower friction than uncoated catheters. Several factors influence the level of friction force exerted by a catheter and may explain why one type of hydrophilic-coated catheter performs better than another in this respect. Among these are the smoothness and evenness of the catheter determined by the outer layer of coating. Other important factors are the osmolality of the catheter coating [9,10] as well as the adherence of the catheter to the urethral mucosa [10,11]. Furthermore, it is possible that the shape of the drainage eyes has an impact on the level of friction exerted by a catheter at withdrawal. However, one study showed no significant difference in withdrawal friction force measured in rabbits for catheters with and without drainage eyes but otherwise identical [9]. In this study it was shown that both of the tested hydrophilic-coated catheters caused significantly less haematuria following catheterisation compared to the uncoated catheter. This result confirms the previous finding that the number of episodes of microscopic haematuria was significantly (p < 0.05) reduced in patients using hydrophilic-coated catheters compared to the patient group using uncoated catheters [5]. This may benefit patients on CIC, since 74% of patients experience initial bleeding when starting on a selfcatheterising CIC regimen, and 28% complain of persistent urethral bleeding 3 months after starting CIC with uncoated catheters [12]. To summarise the results of the friction force and haematuria measurements in this study, it was shown that only one of the hydrophilic-coated catheters performed better than the gel-lubricated uncoated catheter in terms of withdrawal friction force, whereas both hydrophilic-coated catheters performed better than the uncoated catheter with respect to haematuria. Thus, there is no direct correlation between withdrawal friction force and haematuria following catheterisation. In other words, increased friction does not necessarily lead to a higher degree of haematuria, but may cause urethral damage of a different nature. Haematuria measured after catheterisation can be characterised as an acute form of urethral trauma, whereas irritation of the mucosa caused by friction may be followed by subsequent inflammation [4] giving rise to complications in the long term. Due to the crossover design we could not associate the bacteriological urine analyses in this study with any specific type of catheter. Incidence of bacteriuria and symptomatic urinary tract infection has previously been suggested to be decreased in patients using hydrophilic-coated catheters for intermittent catheterisation compared to patients using uncoated catheters [2,13,14]. Concerning the subjective catheter evaluation, the hydrophilic-coated catheters performed better than the uncoated catheter with regard to all the subjective parameters tested, including sensation during insertion and withdrawal of the catheter and discomfort during micturition after catheterisation. Of the two hydrophilic catheters, SpeediCath 1 obtained better scores than LoFric 1. It has previously been shown that patients on a CIC regimen prefer hydrophiliccoated catheters to uncoated catheters. The main reasons for this preference are comfort of insertion, convenience and ease of handling [5,6]. The readyto-use concept of the SpeediCath 1 catheter has also been scored significantly better compared to LoFric 1 with regard to ease of use, discretion and speed of catheterisation [15]. 5. Conclusion The findings in this study indicate that using hydrophilic-coated catheters for intermittent catheterisation reduces urethral micro trauma as determined by the level of haematuria. In addition, hydrophilic-coated catheters were preferred by the participants in this study. However, the hypothesis that hydrophilic-coated catheters in general exert less urethral friction than uncoated catheters must be rejected. Although the SpeediCath 1 hydrophilic-coated catheter exerted a significantly lower mean withdrawal friction force than both InCare 1 Advance Plus and LoFric 1, the other hydrophilic-coated catheter, LoFric 1, was found to exert a significantly higher withdrawal friction force than the gel-lubricated uncoated catheter. Acknowledgments The authors wish to thank research nurse Anne- Grethe Rasmussen and research nurse, MSc Karen Rene Pape as well as all other persons involved in carrying out this study. The primary author is funded by a research grant for a PhD-study from Coloplast A/S. The study was sponsored by Coloplast A/S.

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