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Anesth Analg 2004;99:177-182
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000118101.94596.A0

CRITICAL CARE AND TRAUMA

Jukka Takala Section Editor

Colonization and Bloodstream Infection with Single- Versus Multi-Lumen Central Venous Catheters: A Quantitative Systematic Review

Mathias Zürcher, MD, Martin R. Tramèr, MD DPhil, and Bernhard Walder, MD

Division of Surgical Intensive Care and the Center for Evidence-Based Critical Care, Anesthesia and Pain Treatment, Division of Anesthesiology, Geneva University Hospitals, Geneva, Switzerland

Address correspondence and reprint requests to Mathias Zürcher, MD, Department of Anesthesiology, University of Basel, Kantons- spital, CH-4031 Basel, Switzerland. Address email to zumthis{at}bluewin.ch


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
There is a controversy as to whether the number of lumens in the central venous catheters may impact the incidence of catheter-related bloodstream infection. We performed a systematic search (MEDLINE, PREMEDLINE, Cochrane Library, EMBASE, BIOSIS Previews, CINAHL, HealthSTAR/Ovid healthstar, bibliographies, any language, to April, 2003) for full reports on randomized comparisons of single-lumen and multi-lumen catheters. Trials had to report on dichotomous data of catheter colonization or bloodstream infection. Meta-analyses were performed using a fixed effect model. Data were expressed as odds ratio (OR) and number-needed-to-treat (NNT) with 95% confidence interval (CI). Five randomized trials (1987–1995) with data on 255 single-lumen and 275 multi-lumen catheters were analyzed. Average insertion times were 8 to 21 days with multi-lumen catheters and 9 to 24 days with single-lumen catheters. In 4 trials, 23 of 176 (13.1%) multi-lumen and 26 of 177 (14.7%) single-lumen catheters were colonized (OR, 0.92; 95% CI, 0.49–1.72). In 5 trials, bloodstream infection occurred with 23 of 275 (8.4%) multi-lumen and with 8 of 255 (3.1%) single-lumen catheters (OR, 2.58; 95% CI, 1.24–5.37; NNT, 19; 95% CI, 11–75). For every 20 single-lumen catheters inserted, one bloodstream infection will be avoided that would have occurred had multi-lumen catheters been used. The risk of catheter colonization is not decreased. Although these conclusions are based on limited data, single-lumen catheters should be used whenever feasible.

IMPLICATIONS: Each catheter that is placed into a central vein may induce some morbidity: complications are mechanical, thrombotic, and infectious. Catheter-related bloodstream infection is the most important complication. This systematic review of randomized controlled trials suggests that for every 20 single-lumen catheters inserted, one bloodstream infection would be avoided that would have occurred had multi-lumen catheters been used.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusion
 References
 
Insertion of a central venous catheter (CVC) is a common procedure; the prevalence is about 6% of the hospitalized population (1). However, each catheter placed into a central vein may induce some morbidity: complications are mainly mechanical (2), thrombotic (3), and infectious (4). Among those, catheter-related bloodstream infection is perhaps the most important complication.

Catheter-related bloodstream infection is the second most important cause of nosocomial infection in the intensive care unit (ICU) (5–7) and considerably increases costs of hospitalization (8–11). Up to 90% of catheter-related bloodstream infections originate from CVCs (12). Bacteremia occurred in 5% of patients with ≥48 h ICU stay in a case-control study; in 1.5% of them, there was a confirmed catheter-related bloodstream infection (11). The median excess length of stay for ICU survivors was 9.5 days and the average excess mortality in patients with catheter-related bloodstream infection was 11.5% (11); however, excess mortality was not observed in all investigations (9,10,13).

Proposed strategies to decrease the risk of catheter-related bloodstream infection are as follows: rigorous and strict hygienic barriers (14), the choice of the subclavian venous access (2), correct catheter dressing (15), tunneling of catheters (16), use of heparin after insertion (17), and antiinfective treatment of the catheters, for instance with chlorhexidine-silver sulfadiazine (18) or with antibiotic coating (19).

Another potential option for the prevention of catheter-related bloodstream infection is the limitation of the number of lumens of the catheters, assuming that an increasing number of lumens enhances the likelihood of multiple manipulations and thus of subsequent infection. However, there is a controversy as to whether the number of lumens of CVCs may have an impact on catheter-related bloodstream infections (20–24); indeed, authoritative conventional review articles came to the conclusion that the risk of infection was not reduced with the use of single- compared with multi-lumen catheters (23,24).

The aim of this quantitative systematic review was to test whether single- compared with multi-lumen CVCs had an impact on catheter colonization and catheter-related bloodstream infection.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusion
 References
 
Our primary hypothesis was that multi-lumen catheters increased the risk of infection. An extensive search of the literature without language restriction was performed using MEDLINE (PubMed), PREMEDLINE, BIOSIS Previews, CINAHL, HealthSTAR/Ovid Healthstar, Embase, and the Cochrane Controlled Trials Register. The date of the last electronic search was April 16, 2003. Key words used alone or in combination were central venous catheter, multi-lumen, double-lumen, triple-lumen, infection, complication, prospective, catheter-related infection, risk, and random*. The search was limited to adult 19+ and human. Bibliographies of retrieved reports and of relevant review articles were checked (21–25). Swiss experts in the field of catheter-related infection were asked for further relevant information, including unpublished data or data from the gray literature (for instance, abstracts). Manufacturers of CVCs were not contacted. If there was ambiguity about the original data we contacted the investigators and asked for clarification.

We included reports of randomized controlled trials in adults that compared single-lumen CVCs with multi-lumen (≥2 lumens) CVCs and that reported dichotomous data on catheter colonization or catheter-related bloodstream infection. There was an intention to include data from abstracts if study design was appropriate and data reporting was adequate. All anatomical sites of insertion were considered. However, the catheters had to be inserted percutaneously. Data on tunneled catheters, antiinfective coated catheters, catheters inserted for home infusion therapy, and pulmonary artery, dialysis, or other special catheters (for instance, inferior vena cava catheters for plasmapheresis) were excluded. Title and abstracts of all retrieved papers were assessed for potential relevance; this was done independently by two authors (MZ, BW). We obtained hard copies of all relevant papers.

Catheter colonization was defined as a documented growth from a proximal or distal catheter segment of either 15 or more colony-forming units in a semi-quantitative culture (26) or more than 103 colony-forming units in a quantitative culture (27,28). This definition was valid for the purpose of this study independent of whether the external surface only or both the internal and the external surfaces of the catheters were cultured. Catheter-related bloodstream infection was defined as the presence of the same organism isolated from a (semi-) quantitative culture of a catheter segment and from the patient’s blood (withdrawn from a different site than the site of CVC) in the absence of another source of infection (29), independent of the presence of accompanying clinical symptoms (i.e., sepsis). Catheter-related bloodstream infection was regarded as the more relevant end-point in this context. Insertion site infection was not considered as a valid end-point because there is no objective and generally accepted definition for this end-point and its clinical relevance is uncertain.

All authors independently read the included papers and critically appraised their methodological quality using the validated three-item, 5-point Oxford scale (30). Allocated scores were compared; consensus was reached by discussion. We extracted information on the number of catheters, indication for CVC placement, insertion site, end-points, clinical setting, and average insertion times of the catheters from each study and entered the data into standardized data sheets. Average insertion time was defined as the average delay between catheter insertion and catheter removal.

Dichotomous data on colonization and bloodstream infection per number of inserted CVCs were analyzed. As there were zero cells in some trials (i.e., no event was reported in one or both study arms) we calculated Peto odds ratios (OR) with 95% confidence interval (CI). Because all combined data were homogenous (P > 0.1) we used a fixed effect model throughout. As an estimate of the clinical relevance of any difference between single- and multi-lumen catheters we calculated the number-needed-to-treat (NNT) with 95% CI using weighted means of the event rates (31). As in previous similar analyzes (32), there was an agreement that an NNT ≤50 to prevent one catheter-related bloodstream infection with single-lumen compared with multi-lumen catheters was a clinically relevant improvement. This degree of risk reduction would justify the promotion of single-lumen CVCs. Data from individual trials were displayed using both forest plots (RevMan version 4.1, Cochrane Library, Oxford, UK) to show relative benefit of single-lumen compared with multi-lumen catheters and event rate scatters (33) to illustrate variability in incidence of outcomes. On event rates scatters, data points below the line of equality would suggest relative benefit with single-lumen catheters.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusion
 References
 
We screened 33 reports (31 full reports, two abstracts). Twenty reports were analyzed in detail (Fig. 1). Of those, 15 were subsequently excluded; 9 full reports (34–42) and 2 abstracts1,2 were not on randomized trials, 3 full reports (37,43,44) did not fulfill our inclusion criteria, and 1 paper (45) did not report on end-points that were relevant for the purpose of this systematic review. We contacted all authors of the included reports and asked for additional information; none of them answered. One of 5 experts responded to our enquiry but was unable to provide any additional relevant data.



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  		Figure 1. Flow chart.

 
We eventually analyzed data from 5 randomized controlled trials, published as full reports between 1987 and 1995 (46–50) (Table 1). The median Oxford score was 2; 1 trial scored 1, 2 scored 2, and 2 scored 3. There were data on 530 CVCs (275 multi-lumen, 255 single-lumen). All catheters were polyurethane devices. The insertion site was subclavian (46,48,50) or both subclavian and internal jugular (47); in one trial, the insertion site was unclear (49). In one trial the average insertion time of multi-lumen catheters was significantly shorter compared with single-lumen CVCs (9.1 ± 5 days versus 11.6 ± 6 days, P = 0.04) (47); in all other trials, average insertion times were similar. In all trials, full sterile barrier control, skin disinfecting procedures, catheter handling, and dressing protocols were reported.


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  		Table 1. Characteristics of Included Trials
 
Four trials (353 catheters) reported on catheter colonization (Fig. 2) (47–50). Two different techniques for bacterial culture were used, the roll plate technique (26) and the broth dilution technique (28) (Table 1). In one trial, there was a statistically significant benefit in favor of single-lumen catheters (50). Two trials were in favor of multi-lumen catheters although the results were not statistically significant (47,48). Finally in one trial there was equivalence (50). When data from all 4 trials were combined (P for heterogeneity 0.1), 23 of 176 (13.1%) multi-lumen and 26 of 177 (14.7%) single-lumen catheters were colonized. This difference was not statistically significant (OR, 0.92; 95% CI, 0.49–1.72).



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  		Figure 2. Catheter colonization. On the event rate scatter, symbol areas are proportional to the size of the trials. OR = odds ratio; CI = confidence interval.

 
All trials reported on presence or absence of catheter-related bloodstream infection (Fig. 3). In 2 trials, there was a statistically significant benefit in favor of single-lumen catheters (46,50). In 2 trials, there was equivalence (47,48). In 1 study, no infection was reported (49). When data from all 5 trials were combined (P for heterogeneity 0.3), there were 23 of 275 (8.4%) bloodstream infections with multi-lumen catheters and 8 of 255 (3.1%) with single-lumen catheters. This difference was statistically significant (OR, 2.58; 95% CI, 1.24–5.37; NNT, 19; 95% CI, 11–75).



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  		Figure 3. Catheter-related bloodstream infection. On the event rate scatter, symbol areas are proportional to the size of the trials. OR = odds ratio; CI = confidence interval.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusion
 References
 
There is some evidence that the risk of catheter-related bloodstream infection may be less with single-lumen compared with multi-lumen CVCs. Approximately one in 20 single-lumen CVCs will not lead to a bloodstream infection that would have occurred had multi-lumen catheters been used. According to our pre hoc definition, this degree of benefit is of clinical relevance. Similar absolute risk reductions for the prevention of catheter-related bloodstream infection have been described with the use of antibiotic or chlorhexidine-silver sulfadiazine coated CVCs (32) or with the subclavian compared with the internal jugular approach (2).

Because this result was based on a limited number of trials that tested a relatively small number of catheters, it is of importance to identify a biological basis that supports a benefit with single-lumen catheters. There are two arguments here. First, microorganisms do attach to foreign material; in contact with plastic surfaces they produce a protective multilayer biofilm, and within this film, they can survive (51). Depending on the number of lumens, multi-lumen CVCs have a two to three times larger intraluminal surface compared with single-lumen catheters. This relatively larger intraluminal surface may lead to increased bacterial growth and subsequently to an increased risk of bloodstream infection. Second, it can be hypothesized that with single-lumen catheters there is a decreased risk of bacterial contamination resulting from a reduced number of manipulations, infusion devices, and stopcocks, particularly when sterile barriers are not maintained correctly. Thus, again, the risk of contamination of the internal surface of the catheter would be minimized. There was, however, no difference in the rates of colonization between multi-lumen and single-lumen CVCs. This may be explained by the bacterial culture techniques that have been used in these trials. Both the roll plate technique and the broth dilution technique detect well bacterial growth on the external surfaces of catheters but less so on internal surfaces (52). Thus, it may be that the incidence of colonization was generally underestimated in these trials and that the impact of this underestimation was largest with multi-lumen catheters because of their relatively larger internal surface compared with single-lumen catheters.

The average methodological quality of these trials was limited. A major problem was the lack of blinding, which may be difficult or even impossible in this setting. There is empirical evidence that inadequate blinding may lead to observer bias, which, in turn, may lead to the overestimation of the effect of a treatment (53). It is unclear how observer bias may apply here. We cannot exclude, though, that in these open studies, the beneficial effect of single-lumen catheters was exaggerated to some extent.

The strength of evidence arising from these 5 randomized trials may be regarded as scant, and at best as hypothesis generating. Large randomized trials are warranted to confirm these data. However, to achieve a statistically significant result with a presumed absolute risk reduction of 4% to 5% for bloodstream infection, about 400 patients per group are needed. The largest trial included only 177 patients (46).

Future trials should take into account potential confounding factors that have not been controlled for in most of these studies. Among those are skills and performance of the operators in placing the catheters (54), the number of punctures before successful catheter placement (55), the number of manipulations on the administration set (21), antibiotics after placement of the catheter (56), and the type of infusions that are used and their risk of contamination (57). Finally, a more global view on the efficacy of antiinfective strategies for CVCs is needed. Although it has been suggested that colonization was an essential step in the pathogenesis of catheter-related bloodstream infection (5,58), colonization and even bloodstream infection may be regarded as surrogate end-points. For rational decision making, we need additional relevant data; for instance on length of hospital stay, cost, and mortality.

The use of single-lumen catheters is a simple and inexpensive method. This begs the question as to whether it was worthwhile to combine this procedure, if it was effective, with other preventive strategies to further decrease the risk of CVC-related infection. Relative efficacy and cost-effectiveness of such combined strategies, however, are not well investigated. Finally, we need to know more about which patients would profit most from a multimodal antiinfection approach.


   Conclusion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
References
 
There is some evidence, from 5 randomized trials with data on 530 CVCs, that for every 20 single-lumen catheters inserted, one bloodstream infection will be avoided which would have occurred had multi-lumen catheters been used. We were able to analyze a limited number of relevant trials only; also, the size and the methodological quality of the trials were not always satisfactory. Thus, large randomized trials of adequate methodology are needed to confirm this result and to clearly define the role of single-lumen catheters as part of a multimodal preventive antiinfection program. In the meantime, it may be reasonable for patients who need a CVC to choose a single-lumen catheter whenever there is no indication for a multi-lumen catheter.


   Acknowledgments
 
Supported, in part, by a PROSPER grant (3233–051939.97/2 to MRT) from the Swiss National Science Foundation.


   Footnotes
 
1 Kovacevich DS, Faubion WC, Braunschweig CL, et al. Prevalence of catheter sepsis in parenteral nutrition patients with triple lumen vs. single lumen catheters [abstract]. JPEN J Parenter Enteral Nutr 1988;12:23S. Back

2 Pomp A, Varella L, Caldwell MD, et al. Catheter-related sepsis: single lumen catheters (SLC) vs triple lumen catheters (TLC) [abstract]. JPEN J Parenter Enteral Nutr 1988;12:23S. Back


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 

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Accepted for publication January 5, 2004.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2004 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press