Use of non-pharmacological interventions during urinary catheter insertion for reducing urinary tract infections in non-immunocompromised adults. A systematic review

Introduction: Catheter-associated urinary tract infections (CAUTI) account for up to 30% of hospital -acquired infections. In this regard, several studies have reported the use of non-pharmacological interventions during urinary catheter insertion aimed at reducing the occurrence rate of CAUTI. Objective: To assess the safety and effectiveness of non-pharmacological interventions during urinary catheter insertion aimed at reducing the risk of contracting infections in non-immunocompromised adults. Materials and methods: A literature review was conducted in the MEDLINE, Embase, and LILACS databases. Only randomized clinical trials comparing the use of non-pharmacological interventions to placebos, pharmacological interventions, or no intervention during catheter insertion were included. Results: Eight studies were retrieved (8 718 participants). Based on the evidence found in the review (low-quality and very low-quality evidence according to the GRADE system), using non-pharmacological interventions reduces the frequency of asymptomatic bacteriuria episodes (RR 0.67, 95%CI 0.48-0.94; 7 studies) or mild adverse events (RR 0.84, 95%CI 0.74-0.96; 2 studies), but does not reduce the occurrence rate of symptomatic urinary tract infections (RR 0.90, 95%CI 0.61-1.35; 4 studies) or improves quality-of-life scores (MD –0.01 EQ-5D scale; 95%CI (-0.03)-(0.01), 1 study). Conclusion: The use of non-pharmacological interventions during urinary catheter insertion does not pose any risk at all. Instead, it could help reduce the occurrence rate of infections associated with this procedure, such as asymptomatic bacteriuria and mild adverse events. However, there is very little evidence (in fact, low and very low-quality evidence) to make conclusions on the effectiveness of these interventions.


Introduction
Catheterization is a common procedure that consists of the insertion of a latex, polyurethane, or silicone tube into the bladder to drain its contents. 1 Urinary catheters can be indwelling or placed intermittently depending on the indications and the patient's condition. Intermittent catheters are inserted every 6 to 8 hours, 2 while indwelling catheters are inserted for a period of time greater than 24 hours, and are usually connected to a collection bag. 3 Indwelling catheterization is typically used in patients with pathologies such as prostatic hyperplasia, neurogenic bladder, urinary retention, severe urinary incontinence, as well as critically ill patients 4 and those with pressure ulcers in the sacral region, or with contaminated perineal lesions associated with incontinence. 5 Urinary catheterization is a minor procedure undertaken in up to 25% of all hospitalized patients. 6 It carries substantial risks and causes high morbidity and mortality secondary to bacteremia, as well as longer hospital stays and higher resource consumption. 7 Catheter-associated urinary tract infection (CAUTI) accounts for up to 30% of health-care associated infections. 7 In Latin America, CAUTI is the third leading cause of nosocomial infections and its incidence is estimated at 8.9 cases per 1 000 days of exposure to this device. 6 In Colombia, the estimated prevalence is 12% to 45%, which makes it one of the top five infections reported in the country. 6 In Bogotá, a prevalence of 16.1% was reported for the 2012-2013 period, with an incidence rate of 3.9 cases per 1 000 days of exposure. 6 Since urinary catheterization carries substantial risks, multiple interventions have been described with the aim of reducing the occurrence of infectious processes. Non-pharmacological interventions include staff training in catheter insertion and care. 8 Access to guidelines and algorithms allows standardizing interventions that avoid variability among healthcare staff and guide the timely removal of unnecessary catheters. 7,9 Hand washing before and after catheter insertion and manipulation reduces non-saprophytic microflora without affecting the saprophytic microflora of the skin. 5,7 Using an aseptic technique, sterile equipment and supplies during the preparation of the catheter insertion area and during the insertion, using barrier measures such as sterile gowns and gloves; 10 and the use of antiseptics for cleaning the urinary meatus help reduce microbial load and the entrainment of microorganisms. 5,11 In addition, the lubricant applied prior to insertion contributes to bladder neck relaxation, facilitating the passage of the catheter, and also prevents urethral trauma, false passages and pain. 10 Inserting a catheter of the smallest possible size can minimize urethral trauma and lead to a more effective drainage, 5,12 while using a closed drainage system makes it more difficult for microorganisms to colonize the urethral meatus intraluminally. 13 Regarding pharmacological interventions, silicone catheters are recommended for patients requiring a long-term urinary catheter and in those with frequent obstruction of the device. 7 Antimicrobial-coated catheters are used in patients with a CAUTI that does not decrease with the application of primary strategies. Finally, the consumption of blueberries, 14 lactobacilli 15 and Chinese herbal medicines 14 has also been proposed to prevent urinary infections.
Since the use of catheters in clinical practice is heterogenous and considering the frequency of adverse events and the appearance of infections associated with their insertion and use, this systematic review seeks to assess the effects of non-pharmacological interventions aimed at reducing the probability of CAUTI in the adult population. This will help develop policies designed to standardize the care of adult patients with urinary catheterization.

Materials and methods
The report was developed following the recommendations suggested by the Cochrane Handbook (CHB) 16 and in accordance with the PRISMA statement. 17 Review methods were established before conducting the literature search, which is detailed at http://www.crd.york.ac.uk/ PROSPERO/display_record.php?ID=CRD42017051553. Ethical approval was not required because this is a secondary study.
An attempt was made to identify as many relevant randomized controlled trials (RCTs) as possible, regardless of their language of publication. To this end, the Information Specialist of The Cochrane STI Group was contacted to conduct a complete search strategy, which was constructed using controlled vocabulary and text terms. The search was conducted in the MEDLINE, EMBASE, and LILACS databases. Grey literature was also consulted through the references listed in the included studies. The search was updated to September 30, 2016 (available at: https:// www.crd.york.ac.uk/PROSPEROFILES/51553_STRAT-EGY_20161121.pdf) and citations were exported to EndNote version X6 (Thomson Reuters, New York, NY, USA). All published RCTs were included with no language restrictions.
The participants in the trials were non-immunocompromised men and non-pregnant women that required an indwelling urinary catheter as part of their inpatient or outpatient medical treatment. Indwelling urinary catheters are as those inserted for at least 24 hours in the urinary tract. The intervention of interest was the use of any non-pharmacological intervention during catheter insertion versus the use of placebo, or pharmacological interventions, or no intervention.
The primary outcomes were symptomatic urinary infection, time elapsed until the first episode of urinary infection, recurrent infection, bacteremia, asymptomatic bacteriuria, and major adverse effects associated with the intervention. The main secondary outcomes were satisfaction of participants, quality of life, mild adverse events, and cost-effectiveness of the intervention.
First, two authors (XSM and CFGA) selected the studies individually, and then, through consensus, they made the final selection of studies to be included in the systematic review. In addition, the other two authors (JAG and JLMV) assessed the risk of bias of the included RCTs using the tool suggested in the CHB: 16 sequence generation and allocation concealment, blinding of participants, incomplete outcome data, selective reporting, and other risks of bias. Disagreement was resolved by consensus among all authors. All domains were assessed as low, high, or unclear risk of bias. The GRADE system was used for rating the quality of the evidence.
Results are presented as risk ratios (RR) with 95% confidence intervals (CI) and mean differences. I 2 statistic and Chi 2 test values were used to assess statistical heterogeneity, which was considered relevant if the I 2 statistic was greater than 40% and if there was a low p-value (less than 0.10) in the Chi 2 test for consistency. Statistical analyses were performed using Rev Man, 18 with fixed-effect meta-analysis for combining data, unless there was substantial heterogeneity, while a random-effects model was implemented if there was clinical or significant statistical heterogeneity.

Results
The searches yielded 311 references, and 214 were screened after removing duplicates. Of those, the full texts of 30 references were reviewed. A total of 8 studies met the inclusion criteria; 19-26 12 papers were excluded because they were not RCTs, 6 trials implemented a different intervention and finally, 4 studies recruited a different kind of population. The following PRISMA diagram illustrates the selection process ( Figure 1). For excluded RCTs and the rationale for exclusion, see Appendix A.
The selected RCTs were published from 1985 to 2012 and recruited participants from Sweden, the United Kingdom, Hong Kong, New Zealand, the USA and Belgium; 2 of those studies were funded by the industry. 21,25 Retrieved studies involved 8 718 men and women with an age range between 20 and 95 years, who required long-term catheterization (>24 hours) during their hospital stay due to general, 20,24 cardiac, 22 orthopedic 25 or elective urologic surgery; 26 3 studies did not include information in this regard. 19,21,23 The studies excluded patients with current or previous urinary tract infection, recent exposure to antibiotics, history of diabetes or pelvic radiotherapy, or with a recent illness (Table 1).  The intervention most commonly implemented was silicone-coated latex catheter in 5 studies; 21,23-26 2 studies described sterile catheterization as the intervention; 19,20 and the remaining trials used non-coated silicone catheters. 22 The comparator in 6 studies was non-coated silicone urinary catheter [21][22][23][24][25][26] and in the other 2 it was clean/non-sterile catheterization technique. 19,20 Sterile catheterization is the process of cleaning the urethral meatus utilizing an antiseptic aqueous solution and avoiding contact with the practitioner's gloves. The catheter is inserted following a non-touch technique and using forceps after lubrication with sterile lignocaine gel. On the other hand, participants assigned to non-sterile catheterization used sterile water and non-sterile gloves. 19,20 22 According to the GRADE system, publications bias should be assessed using a funnel plot and asymmetry statistical tests if 10 or more studies are included in a systematic review or a meta-analysis; therefore, since only 8 studies were included in this review, a funnel plot was not required to assess publication bias. The RCTs included (n=8) had limitations regarding the use of risk of bias tools, which are detailed in Figure 2 and Appendix B. In

Identification
The included RCTs assessed at least one predetermined outcome, with some minor differences in the definition of the results between papers. A total of 7 studies reported bacteriuria as the primary outcome 19-21,23-26 using as threshold 10 5 colony-forming units (CFU) per milliliter (mL), except for one study 24 that defined a lower threshold (>1.000 CFU/mL). Three studies reported symptomatic urinary infection -defined as penile discomfort and purulent urethral discharge 22 reported by the patient or the caregiver-, bacterial colonization in urine, 20 or the presence of symptoms accompanied by antibiotic prescription. 23 Urine specimens were collected at the time of catheterization, [19][20][21]25 at the time of catheter removal, 21,24,26 or within 7 to 14 days 20,23,25 after catheterization. The secondary outcomes reported by the trials were quality of Rev. Fac. Med. 2020 Vol. 68 No. 1: 24-33 this regard, 4 trials 19,22,23,25 implemented a valid sequence generation method and 3 established an adequate allo-cation concealment process (Figure 2), 19,22,23,25 making selection bias unclear.  Regarding blinding, 5 studies 19-21,24,26 did not report the method implemented. However, the studies were considered to be at low risk of detection and performance bias since the results were objectively appraised (i.e., culture) and, therefore, the lack of blinding is unlikely to affect confidence in the results. One study 22 was masked to the allocated intervention because of the similarity of the interventions, making performance and detection bias unlikely. Finally, 23,25 the participants of 2 trials were not masked to the intervention because of the distinctive appearance of the catheters; based on the subjective nature of some outcomes (i.e., mild adverse events of the intervention), these RCTs were considered as having high risk of performance and detection bias.
With respect to possible attrition bias, 2 RCTs 22,24 appropriately mentioned the exclusions (<20%) and the reasons were balanced between the arms, making incomplete outcome data bias unlikely. For 6 studies, trial protocols were not available and were assessed as having unclear risk of bias. [19][20][21][22]24,26 Finally, all RCTs were at low risk of other potential sources of bias. Table 2 presents a detailed description of the quality of the evidence. * Two trials have high risk of detection, attrition and reporting bias. † Heterogeneity I 2 =63%. ‡ CI overlaps the line of no difference and failed to exclude appreciable benefit or harm. ** Relevant heterogeneity I2= 71%. † † Heterogeneity I2=0%. ‡ ‡ High risk for detection, attrition, and selective reporting. Source: Own elaboration.
Low-quality evidence showed that, compared to the control group, the use of non-pharmacological intervention does not seem to decrease the frequency of symptomatic urinary infections 20   Carappetti et al. 19 measured resource and capital expenditure associated with the implementation of sterile interventions compared to clean catheterization. The recruited participants underwent preoperative urethral catheterization and the direct costs were estimated based on the supplies utilized: gloves, sterile gown, catheter pack, lignocaine gel, vaginal gel, sterile water, 10-milliliter syringes, catheter bag, Foley catheter, scrub solution, and skin preparation. Compared with clean catheterization, sterile technique doubled care-associated costs, as the total cost per participant was close to GBP 7.49 versus GBP 3.06, respectively, in 1994. This study did not assess indirect or long-term intervention-related costs.

Non-pharmacological intervention
To explore heterogeneity, a subgroup analysis was performed for the asymptomatic bacteriuria outcome.
The tests for subgroup effect were not significantly different when the source of heterogeneity was explored (p=0.54, data not shown). Subgroup analyses did not explain the variability in the summary effect measures for the asymptomatic bacteriuria outcome, so these findings should be interpreted with caution. The outcomes symptomatic urinary infection, time elapsed until the first episode of urinary tract infection and major adverse effects derived from the intervention were not analyzed because of the sparse information provided by the RCTs included in the present review.

Discussion
This systematic review retrieved low-quality evidence to support the implementation of non-pharmacological interventions at the time of urinary catheter insertion to reduce the risk of infection in non-immunocompromised adults with indwelling catheterization. Regardless of the comparison, non-pharmacological interventions seem to reduce the frequency of asymptomatic bacteriuria episodes and the rate of mild adverse events.
One of the strengths of this systematic review is that its methodology was planned, developed and published at PROSPERO before conducting it, and all the methods that were established at that time were followed while doing the review, namely, a comprehensive literature search without language or date restrictions, two reviewers in charge of the selection of studies, data extraction and bias risk assessment using the tool suggested in the CHB; 16 evidence ranking by means of the GRADE approach; and the use of subgroup analyses and methods for statistical analysis.
One of the weaknesses of the present review is that the quality of the evidence found was very low according to the GRADE system; therefore, further research is highly likely to change the conclusions presented here. On the other hand, the RCTs included were heterogenous and publication bias was not assessed using a funnel plot due to the recommendation of the GRADE system regarding the detection of this type of bias when less than 10 studies are included in a meta-analysis or a systematic review.
There were no other systematic reviews evaluating the impact of non-pharmacological interventions for catheter insertion in cases of urinary tract infection that require long-term catheterization. Consistent with this review, a Cochrane review concludes that the use of silver-coated catheters reduces the frequency of asymptomatic bacteriuria, but the studies reviewed there only assessed short-term catheterization. 27

Conclusion
Very low-quality evidence shows that non-pharmacological interventions at the time of urinary catheter insertion in non-immunocompromised adults could reduce the frequency of asymptomatic bacteriuria episodes and mild adverse events, without reducing the rate of symptomatic urinary infections or improving quality-of-life scores.

Conflicts of interest
None stated by the authors.

Funding
This study was financed through a HERMES grant (code 33595) awarded by the Faculty of Nursing of Universidad Nacional de Colombia, Bogotá Campus, as stated in Resolution 073 of 2016 (Act 11, May 12, 2016).