Chapter 16. Prevention of Intravascular Catheter-Associated Infections (continued)
Subchapter 16.3. Use of Chlorhexidine Gluconate at the Central Venous Catheter Insertion Site
Microbial populations on the skin are routinely suppressed with antiseptic agents prior to catheter insertion. Using an antiseptic solution for skin disinfection at the catheter insertion site helps to prevent catheter-related infections. The physician uses an agent that has antimicrobial properties to thoroughly cleanse the skin just prior to insertion of a central venous catheter. In the United States, povidone-iodine (PI) is overwhelmingly the most commonly used agent for this purpose. Recently, several studies have compared the efficacy of PI and chlorhexidine gluconate (CHG) solutions in reducing vascular catheter-related infections.
Opportunities for Impact
If PI is the most commonly used agent for site disinfection in the United States even though CHG may be superior, substantial opportunity exists for impact by switching to CHG.
The study characteristics of 6 randomized trials48-53 comparing any type of CHG solution with PI solution for vascular catheter site care are shown in Table 16.3.1. The mean duration of catheterization for the CHG and PI groups was comparable in most of the studies. There was no significant difference in the sites at which catheters were inserted between the CHG and PI groups. Several formulations of CHG were used, including9,12-14 an alcoholic solution and an aqueous solution. All studies used 10% PI solution for the control arm.
All studies48-53 evaluated catheter colonization (Level 2 outcome) and all but one52 evaluated CR-BSI (Level 1 outcome). All studies evaluating CR-BSI as an outcome required the recovery of the same microbial species from both the catheter segment and a blood culture.
Evidence for Effectiveness of the Practice
Most clinical trials have revealed that the use of CHG solution results in a significant decrease in catheter colonization, but the evidence is not clear for CR-BSI (Table 16.3.2). Most of the individual trials showed a trend in reducing CR-BSI incidence in patients using CHG solution. The lack of significant results may be a result of insufficient statistical power in the individual studies. A formal meta-analysis of the published trials would be valuable in assessing the comparative efficacy of PI versus CHG for central venous catheter site disinfection. Using explicit inclusion criteria and accepted quantitative methods, a meta-analysis54-56 can often help clarify the features of individual studies that have divergent results and increase statistical power since several small studies can be pooled.58
Potential for Harm
Only one study reported adverse effects from the use of either antiseptic solution. Maki et al48 found erythema at the insertion site in 28.3% of catheters in the PI group and in 45.3% of catheters in the CHG group (p=0.0002). However, there was no statistically significant difference in erythema among these 2 groups and those patients whose site was disinfected with alcohol. Hypersensitivity reactions to chlorhexidine-silver sulfadiazine impregnated central venous catheters and to use of CHG for bathing have been reported. Hypersenstivity reactions were not reported in any of the studies, but clinicians should be aware of such potential side effects. Another concern is the development of bacterial resistance. However, there have been few reports of bacterial resistance to CHG despite its widespread use for several decades.
Costs and Implementation
The cost of CHG is approximately twice that of PI with an absolute difference of $0.51 (approximately $0.92 versus $0.41 for a quantity sufficient to prepare a central venous catheter insertion site). If meta-analysis suggests that CHG use is effective in reducing the risk of CR-BSI, a formal economic evaluation of this issue is required.
The use of chlorhexidine gluconate rather than povidone-iodine solution for catheter site care may be an effective and simple measure for improving patient safety by reducing vascular catheter-related infections. Formal meta-analysis and economic evaluations are required before strongly recommending that CHG replace PI for central venous catheter site disinfection in appropriate patient populations.
Table 16.3.1. Characteristics of studies comparing chlorhexidine gluconate (CHG) and povidone-iodine (PI) solutions for vascular catheter site care*
||Number of Catheters (Treatment, Control)
||Mean Catheter Duration in Days (Treatment, Control)
||Catheter-Related Bloodstream Infectionb
|Maki48: 441 ICU patients (2% aqueous CHG solution in 214, PI in 227)
||SQ (>15 CFU)
||CX, NoSource, Sx
|Sheehan49: 189 ICU patients (2% aqueous CHG solution in 94, PI in 95)
||SQ (>15 CFU)
||CX, NoSource, Sx
|Meffre50: 1117 hospital patients (CHG solution of 0.5% alcohol 70% in 568, PI in 549)
||SQ (>15 CFU) or QN (>103 CFU/mL)
||[Local or Sx] or [CX, NoSource]
|Mimoz51: ICU patients (Biseptine®
c vs. PI)
||QN (>103 XFU/mL)
|Cobett and LeBlanc52: 244 hospital patients (0.5% alcohol 70% in 8, PI in 161)
||SQ (>15 CFU)d
|Humar et al53: 3374 ICU patients (0.5% alcohol in 193 and 181/193
||SQ (>15 CFU)
||CX, Molec, NoSource
* CFU indicates colony forming units; CX, same organism or species matched between blood and catheter segment culture; ICU: intensive care units; Local: local signs of infection; Molec: same organism confirmed by molecular subtyping; NA:not available; NoSource: no other source of infection; QN: quantitative; Sx: clinical symptoms of bloodstream infection; SQ: semiquantitative.
a All studies used 10% povidone-iodine solution.
b Catheter segments (or site) cultured and criteria for a positive culture are given in parenthesis.
c Biseptine® consists of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, 4% benzyl alcohol.
d Required one of the following symptoms: fever, erythema, heat at the site, and pain.
Table 16.3.2. Results of Studies Comparing Chlorhexidine Gluconate (CHG) and Povidone-iodine (PI) Solutions for Vascular Catheter Site Care*
||Catheter Colonization (Positive Cultures)
||RR (95% CI)
CHG vs. PI
|Catheter Related Bloodstream Infection
||RR (95% CI)
CHG vs. PI
|Cobett and LeBlanc52a
* CI indicates confidence interval; RR, relative risk.
a Additional information was provided by authors.
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Subchapter 16.4. Other Practices
Practices That Appear Promising
Use of heparin with central venous catheters. Because an association has been shown between thrombus formation and catheter-related infection, clinicians usually use heparin, in a variety of forms: 1) as flushes to fill the catheter lumens between use; 2) injected subcutaneously; or 3) bonded on the catheter. A meta-analysis of 12 randomized trials evaluating prophylactic use of heparin in patients using central venous catheters has shown that prophylactic heparin decreases catheter-related venous thrombosis (Level 2 outcome; RR 0.43, 95% CI: 0.23-078) and bacterial colonization (Level 2 outcome; RR 0.18, 95% CI: 0.06-0.60) and may decrease CR-BSI (Level 1 outcome; RR 0.26, 95% CI: 0.07-1.03).59 Since subcutaneous heparin also offers benefit in reducing venous thromboembolism in certain patient populations (see Chapter 31), this is likely to be a reasonable strategy even though CR-BSIs have not definitely been shown to be reduced. However use of heparin is associated with several side effects, such as heparin-induced thrombocytopenia and bleeding.
Tunneling short-term central venous catheters. Since the primary site of entry for microorganisms on the central venous catheter is the site of cutaneous insertion,60 tunneling the catheter through the subcutaneous tissue may decease the incidence of infection. Several trials have evaluated the effect of tunneling on catheter-related infection. A recent meta-analysis has summarized the potential benefit.61 The meta-analysis included 7 trials and found that compared with patients receiving standard catheter placement, tunneling decreased bacterial colonization (Level 2 outcome; RR 0.61, 95% CI: 0.39-0.95) and decreased CR-BSI (Level 1 outcome; RR 0.56, 95% CI: 0.31-1).61 However, the benefit of tunneling came primarily from one trial using the internal jugular as the site of catheter placement; the reduction in CR-BSI no longer reached statistical significance when data from the several subclavian catheter trials were pooled (RR 0.71; 95% CI 0.36-1.43).61 The authors concluded appropriately that current evidence does not support the routine use of tunneling central venous catheters. This could change if the efficacy of tunneling is clearly demonstrated at different placement sites and relative to other interventions (e.g., antiseptic coated catheters).61
Intravenous antimicrobial prophylaxis. There is no evidence to support the systemic use of either vancomycin62 or teicoplanin63 during insertion of central venous catheters. The randomized studies evaluating the use on intravenous vancomycin or teicoplanin have failed to demonstrate that this intervention reduces CR-BSI (Level 1 outcome).62,63 Given the theoretical risk of developing resistance to the antimicrobial agents used for prophylaxis, this practice is not recommended.
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Final Comment to Chapter 16
Infections due to central venous catheters are common and lead to substantial morbidity and healthcare costs. Several practices will likely reduce the incidence of this common patient safety problem, including the use of maximum sterile barrier precautions during catheter insertion, use of catheters coated with antibacterial or antiseptic agents, and use of chlorhexidine gluconate at the insertion site. Additionally, use of heparin and tunneling of the central venous catheter may prove to be effective in reducing CR-BSI. However, the relative efficacy of these interventions is unclear. Also, a clear and formal delineation of the economic consequences of combining several of these patient safety practices is necessary.
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