Skin antisepsis for reducing central venous catheter‐related infections

Nai Ming Lai; Nai An Lai; Elizabeth O'Riordan; Nathorn Chaiyakunapruk; Jacqueline E Taylor; Kenneth Tan

doi:10.1002/14651858.CD010140.pub2

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 4

Forest plot of comparison: 1 Chlorhexidine versus povidone‐iodine, outcome: 1.1 Catheter‐related BSI.

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Figure 5

Forest plot of comparison: 1 Chlorhexidine versus povidone‐iodine, outcome: 1.3 All‐cause mortality.

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Figure 6

Forest plot of comparison: 1 Chlorhexidine versus povidone‐iodine, outcome: 1.4 Catheter colonisation.

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Analysis 1.1

Comparison 1 Povidone‐iodine (in aqueous solution) versus no skin antisepsis, Outcome 1 Catheter‐related BSI.

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Analysis 1.2

Comparison 1 Povidone‐iodine (in aqueous solution) versus no skin antisepsis, Outcome 2 Catheter colonisation.

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Analysis 2.1

Comparison 2 Chlorhexidine (in aqueous solution) versus no skin antisepsis, Outcome 1 Septicaemia.

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Analysis 2.2

Comparison 2 Chlorhexidine (in aqueous solution) versus no skin antisepsis, Outcome 2 Catheter colonisation.

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Analysis 2.3

Comparison 2 Chlorhexidine (in aqueous solution) versus no skin antisepsis, Outcome 3 Number of patients who required antibiotics during in‐dwelling period of catheter.

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Analysis 3.1

Comparison 3 Alcohol versus no skin antisepsis, Outcome 1 Catheter colonisation.

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Analysis 4.1

Comparison 4 Chlorhexidine versus povidone‐iodine, Outcome 1 Catheter‐related BSI.

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Analysis 4.2

Comparison 4 Chlorhexidine versus povidone‐iodine, Outcome 2 Catheter‐related BSI per 1000 catheter‐days.

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Analysis 4.3

Comparison 4 Chlorhexidine versus povidone‐iodine, Outcome 3 All‐cause mortality.

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Analysis 4.4

Comparison 4 Chlorhexidine versus povidone‐iodine, Outcome 4 Catheter colonisation.

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Analysis 4.5

Comparison 4 Chlorhexidine versus povidone‐iodine, Outcome 5 Catheter colonisation per 1000 catheter‐days.

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Analysis 4.6

Comparison 4 Chlorhexidine versus povidone‐iodine, Outcome 6 Insertion site infection.

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Analysis 5.1

Comparison 5 Chlorhexidine (in aqueous solution) versus alcohol, Outcome 1 Catheter‐related BSI.

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Analysis 5.2

Comparison 5 Chlorhexidine (in aqueous solution) versus alcohol, Outcome 2 Catheter colonisation.

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Analysis 6.1

Comparison 6 Povidone‐iodine (in aqueous solution) versus alcohol, Outcome 1 Catheter‐related BSI.

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Analysis 6.2

Comparison 6 Povidone‐iodine (in aqueous solution) versus alcohol, Outcome 2 Catheter colonisation.

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Analysis 7.1

Comparison 7 Alcohol versus octenidine in alcohol, Outcome 1 Catheter‐related BSI.

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Analysis 7.2

Comparison 7 Alcohol versus octenidine in alcohol, Outcome 2 Catheter‐related BSI per 1000 catheter‐days.

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Analysis 7.3

Comparison 7 Alcohol versus octenidine in alcohol, Outcome 3 Catheter colonisation.

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Analysis 7.4

Comparison 7 Alcohol versus octenidine in alcohol, Outcome 4 Catheter colonisation per 1000 catheter‐days.

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Analysis 7.5

Comparison 7 Alcohol versus octenidine in alcohol, Outcome 5 Skin colonisation.

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Analysis 7.6

Comparison 7 Alcohol versus octenidine in alcohol, Outcome 6 Adverse effects.

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Analysis 8.1

Comparison 8 Chlorhexidine (in alcohol) plus povidone‐iodine (in aqueous solution) versus chlorhexidine (in alcohol), Outcome 1 Catheter colonisation.

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Analysis 8.2

Comparison 8 Chlorhexidine (in alcohol) plus povidone‐iodine (in aqueous solution) versus chlorhexidine (in alcohol), Outcome 2 Catheter colonisation per 1000 catheter‐days.

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Analysis 9.1

Comparison 9 Chlorhexidine (in alcohol) plus povidone‐iodine (in aqueous solution) versus povidone‐iodine (in aqueous solution), Outcome 1 Catheter colonisation.

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Analysis 9.2

Comparison 9 Chlorhexidine (in alcohol) plus povidone‐iodine (in aqueous solution) versus povidone‐iodine (in aqueous solution), Outcome 2 Catheter colonisation per 1000 catheter‐days.

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Analysis 10.1

Comparison 10 Sanosil (hydrogen peroxide and silver) versus water as adjunct to chlorhexidine 2% aqueous bath plus povidone‐iodine aqueous 10% scrub, Outcome 1 Catheter colonisation.

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Summary of findings for the main comparison. Chlorhexidine compared to povidone‐iodine in reducing catheter related infections

Chlorhexidine compared to povidone‐iodine for patients with a central venous catheter
Patient or population: patients with a central venous catheter Settings: hospital inpatients Intervention: chlorhexidine Comparison: povidone‐iodine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of Participants (studies)	Quality of the evidence (GRADE)
	Assumed risk	Corresponding risk
	Povidone‐iodine	Chlorhexidine
Catheter‐related BSI ‐ overall comparison between chlorhexidine and povidone‐iodine (during in‐patient stay)	Study population		RR 0.64 (0.41 to 0.99)	1436 (4 RCTs)	⊕⊝⊝⊝ Very low^b,c
	64 per 1000	41 per 1000 (26 to 63)
	Moderate^a
	46 per 1000	29 per 1000 (19 to 45)
Catheter‐related BSI ‐ subgroup: chlorhexidine in aqueous solution versus povidone‐iodine in aqueous solution	Study population		RR 0.64 (0.32 to 1.28)	452 (2 RCTs)	⊕⊝⊝⊝ Very low^c,d
	86 per 1000	55 per 1000 (28 to 110)
	Moderate
	84 per 1000	54 per 1000 (27 to 108)
Catheter‐related BSI ‐ subgroup: chlorhexidine in alcohol versus povidone‐iodine in aqueous solution	Study population		RR 0.77 (0.39 to 1.53)	503 (2 RCTs)	⊕⊝⊝⊝ Very low^c,d
	70 per 1000	54 per 1000 (27 to 108)
	Moderate
	69 per 1000	53 per 1000 (27 to 106)
Catheter‐related BSI ‐ subgroup: chlorhexidine in alcohol versus povidone‐iodine in alcohol	Study population		RR 0.4 (0.13 to 1.24)	481 (1 RCT)	⊕⊕⊕⊝ Moderate^c
	42 per 1000	17 per 1000 (5 to 52)
	Moderate
	42 per 1000	17 per 1000 (5 to 52)
Primary BSI or clinical sepsis	No studies under this comparison assessed this outcome.
All‐cause mortality ‐ Chlorhexidine in aqueous solution versus povidone‐iodine in aqueous solution Clinical assessment	Study population		RR 1.15 (0.72 to 1.83)	213 (1 RCT)	⊕⊕⊝⊝ low^c,e
	236 per 1000	271 per 1000 (170 to 432)
	Moderate
	236 per 1000	271 per 1000 (170 to 432)
All‐cause mortality ‐ Chlorhexidine in alcohol versus povidone‐iodine in aqueous solution Clinical assessment	Study population		RR 0.8 (0.48 to 1.34)	222 (1 RCT)	⊕⊕⊝⊝ low^c,e
	236 per 1000	189 per 1000 (113 to 316)
	Moderate
	236 per 1000	189 per 1000 (113 to 316)
Mortality attributable the CVC‐related infections.	No studies under this comparison assessed this outcome.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BSI: bloodstream infection; CI: Confidence interval.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
^a'Moderate risk' was calculated from the median control event rate for each outcome. ^bThree of the four included studies had unclear risks of bias in allocation concealment, and all had high risks of bias in blinding of participants and personnel. ^cThe 95% CI was wide. ^dThere was an overall very serious concern on risk of bias that resulted in downgrading of two levels: both studies had unclear risk of bias under allocation concealment and high risk of bias under blinding of participants and personnel, and one study had serious unit of analysis issue as the outcome was reported using catheters as the unit, and the number of catheters analysed exceeded the number of participants by over 50%, reflecting that fact that some patients received multiple catheters during the study, which could have seriously affected the effect estimate. ^eThe single study had unclear risk in allocation concealment, high risk in blinding of patients and personnel which might give rise to performance bias, which in turn might affect the risk of mortality, as well as high risk of attrition bias.

Summary of findings for the main comparison. Chlorhexidine compared to povidone‐iodine in reducing catheter related infections

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Comparison 1. Povidone‐iodine (in aqueous solution) versus no skin antisepsis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Catheter‐related BSI Show forest plot	1	179	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.37, 2.61]

2 Catheter colonisation Show forest plot	1	179	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.53, 1.60]

Comparison 1. Povidone‐iodine (in aqueous solution) versus no skin antisepsis

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Comparison 2. Chlorhexidine (in aqueous solution) versus no skin antisepsis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Septicaemia Show forest plot	1	136	Risk Ratio (M‐H, Fixed, 95% CI)	2.91 [0.31, 27.31]

2 Catheter colonisation Show forest plot	1	124	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.61, 2.59]

3 Number of patients who required antibiotics during in‐dwelling period of catheter Show forest plot	1	136	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.55, 1.27]

Comparison 2. Chlorhexidine (in aqueous solution) versus no skin antisepsis

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Comparison 3. Alcohol versus no skin antisepsis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Catheter colonisation Show forest plot	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.30, 1.85]

Comparison 3. Alcohol versus no skin antisepsis

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Comparison 4. Chlorhexidine versus povidone‐iodine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Catheter‐related BSI Show forest plot	4	1436	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.41, 0.99]

1.1 Chlorhexidine in aqueous solution versus povidone‐iodine in aqueous solution	2	452	Risk Ratio (M‐H, Fixed, 95% CI)	0.64 [0.32, 1.28]
1.2 Chlorhexidine in alcohol versus povidone‐iodine in aqueous solution	2	503	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.39, 1.53]
1.3 Chlorhexidine in alcohol versus povidone‐iodine in alcohol	1	481	Risk Ratio (M‐H, Fixed, 95% CI)	0.40 [0.13, 1.24]
2 Catheter‐related BSI per 1000 catheter‐days Show forest plot	4	1450	Risk Ratio (Fixed, 95% CI)	0.53 [0.30, 0.94]

2.1 Chlorhexidine in aqueous solution versus povidone‐iodine in aqueous solution	1	308	Risk Ratio (Fixed, 95% CI)	0.82 [0.23, 2.93]
2.2 Chlorhexidine in alcohol versus povidone‐iodine in aqueous solution	3	661	Risk Ratio (Fixed, 95% CI)	0.49 [0.25, 0.95]
2.3 Chlorhexidine in alcohol versus povidone‐iodine in alcohol	1	481	Risk Ratio (Fixed, 95% CI)	0.41 [0.06, 2.92]
3 All‐cause mortality Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Chlorhexidine in aqueous solution versus povidone‐iodine in aqueous solution	1	213	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.72, 1.83]
3.2 Chlorhexidine in alcohol versus povidone‐iodine in aqueous solution	1	222	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.48, 1.34]
4 Catheter colonisation Show forest plot	5	1533	Risk Difference (M‐H, Fixed, 95% CI)	‐0.08 [‐0.12, ‐0.03]

4.1 Chlorhexidine in aqueous solution versus povidone‐iodine in aqueous solution	2	452	Risk Difference (M‐H, Fixed, 95% CI)	‐0.09 [‐0.17, ‐0.02]
4.2 Chlorhexidine in alcohol versus povidone‐iodine in aqueous solution	3	600	Risk Difference (M‐H, Fixed, 95% CI)	‐0.04 [‐0.11, 0.03]
4.3 Chlorhexidine in alcohol versus povidone‐iodine in alcohol	1	481	Risk Difference (M‐H, Fixed, 95% CI)	‐0.11 [‐0.17, ‐0.04]
5 Catheter colonisation per 1000 catheter‐days Show forest plot	5	1547	Risk Ratio (Fixed, 95% CI)	0.64 [0.50, 0.81]

5.1 Chlorhexidine in aqueous solution versus povidone‐iodine in aqueous solution	1	308	Risk Ratio (Fixed, 95% CI)	0.69 [0.40, 1.20]
5.2 Chlorhexidine in alcohol versus povidone‐iodine in aqueous solution	4	758	Risk Ratio (Fixed, 95% CI)	0.64 [0.48, 0.85]
5.3 Chlorhexidine in alcohol versus povidone‐iodine in alcohol	1	481	Risk Ratio (Fixed, 95% CI)	0.53 [0.24, 1.17]
6 Insertion site infection Show forest plot	1	242	Mean Difference (IV, Fixed, 95% CI)	‐2.80 [‐9.10, 3.50]

Comparison 4. Chlorhexidine versus povidone‐iodine

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Comparison 5. Chlorhexidine (in aqueous solution) versus alcohol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Catheter‐related BSI Show forest plot	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.02, 2.54]

2 Catheter colonisation Show forest plot	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	0.38 [0.11, 1.33]

Comparison 5. Chlorhexidine (in aqueous solution) versus alcohol

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Comparison 6. Povidone‐iodine (in aqueous solution) versus alcohol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Catheter‐related BSI Show forest plot	1	109	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.21, 5.08]

2 Catheter colonisation Show forest plot	2	169	Risk Ratio (M‐H, Fixed, 95% CI)	1.76 [0.76, 4.09]

2.1 Povidone‐iodine in aqueous solution versus alcohol	1	109	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.49, 3.14]
2.2 Povidone‐iodine‐impregnated adherent film versus alcohol	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	9.0 [0.51, 160.17]

Comparison 6. Povidone‐iodine (in aqueous solution) versus alcohol

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Comparison 7. Alcohol versus octenidine in alcohol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Catheter‐related BSI Show forest plot	1	387	Risk Ratio (M‐H, Fixed, 95% CI)	2.01 [0.88, 4.59]

2 Catheter‐related BSI per 1000 catheter‐days Show forest plot	1	387	Risk Ratio (Fixed, 95% CI)	2.18 [0.54, 8.77]

3 Catheter colonisation Show forest plot	1	322	Risk Ratio (M‐H, Fixed, 95% CI)	2.26 [1.22, 4.21]

4 Catheter colonisation per 1000 catheter‐days Show forest plot	1	322	Risk Ratio (Fixed, 95% CI)	2.23 [0.79, 6.29]

5 Skin colonisation Show forest plot	1	365	Mean Difference (IV, Fixed, 95% CI)	79.00 [32.76, 125.24]

6 Adverse effects Show forest plot	1	398	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.60, 1.20]

Comparison 7. Alcohol versus octenidine in alcohol

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Comparison 8. Chlorhexidine (in alcohol) plus povidone‐iodine (in aqueous solution) versus chlorhexidine (in alcohol)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Catheter colonisation Show forest plot	1	88	Risk Ratio (M‐H, Fixed, 95% CI)	0.19 [0.04, 0.81]

2 Catheter colonisation per 1000 catheter‐days Show forest plot	1	88	Risk Ratio (Fixed, 95% CI)	0.19 [0.06, 0.59]

Comparison 8. Chlorhexidine (in alcohol) plus povidone‐iodine (in aqueous solution) versus chlorhexidine (in alcohol)

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Comparison 9. Chlorhexidine (in alcohol) plus povidone‐iodine (in aqueous solution) versus povidone‐iodine (in aqueous solution)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Catheter colonisation Show forest plot	1	95	Risk Ratio (M‐H, Fixed, 95% CI)	0.15 [0.04, 0.62]

2 Catheter colonisation per 1000 catheter‐days Show forest plot	1	95	Risk Ratio (Fixed, 95% CI)	0.17 [0.05, 0.52]

Comparison 9. Chlorhexidine (in alcohol) plus povidone‐iodine (in aqueous solution) versus povidone‐iodine (in aqueous solution)

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Comparison 10. Sanosil (hydrogen peroxide and silver) versus water as adjunct to chlorhexidine 2% aqueous bath plus povidone‐iodine aqueous 10% scrub

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Catheter colonisation Show forest plot	1	249	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.68, 1.72]

Comparison 10. Sanosil (hydrogen peroxide and silver) versus water as adjunct to chlorhexidine 2% aqueous bath plus povidone‐iodine aqueous 10% scrub

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