Author Contributions
Conceptualization, C.-H.C., Y.-M.C., Y.Y., Y.-J.C., L.-J.Y. and H.-C.Y.; Methodology, C.-H.C., Y.-M.C. and Y.-J.C.; Software, C.-H.C., Y.-M.C. and Y.-J.C.; Validation, C.-H.C., Y.-M.C., Y.Y. and Y.-J.C.; Formal Analysis, C.-H.C., Y.-M.C. and Y.-J.C.; Investigation, X.X.; Data Curation, C.-H.C.; Writing—Original Draft Preparation, C.-H.C.; Writing—Review and Editing, C.-H.C., Y.-M.C., Y.Y. and Y.-J.C.; Writing—Approval, C.-H.C., Y.-M.C., Y.Y., Y.-J.C., L.-J.Y. and H.-C.Y.; Visualization, C.-H.C. and Y.-M.C.; Project Administration, C.-H.C.; Funding Acquisition, C.-H.C.
Figure 1.
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram for the search and identification of the included studies.
Figure 1.
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram for the search and identification of the included studies.
Figure 2.
Forest plot of the overall odds ratios for catheter-related bloodstream infection in the treated group versus the control group. The random model of overall odds ratio showed a significant overall effect of interventions in reducing the risk for developing catheter-related bloodstream infections as compared with the control condition (OR, 0.424; 95% CI, 0.267–0.673; p < 0.001).
Figure 2.
Forest plot of the overall odds ratios for catheter-related bloodstream infection in the treated group versus the control group. The random model of overall odds ratio showed a significant overall effect of interventions in reducing the risk for developing catheter-related bloodstream infections as compared with the control condition (OR, 0.424; 95% CI, 0.267–0.673; p < 0.001).
Figure 3.
Forest plot of the overall odds ratios for exit-site infection in treated group versus the control group. The random model of overall odds ratio for exit-site infection showed a significant overall effect of interventions in reducing the risk for developing exit-site infection as compared with the control condition (OR, 0.627; 95% CI, 0.441–0.893; p = 0.001).
Figure 3.
Forest plot of the overall odds ratios for exit-site infection in treated group versus the control group. The random model of overall odds ratio for exit-site infection showed a significant overall effect of interventions in reducing the risk for developing exit-site infection as compared with the control condition (OR, 0.627; 95% CI, 0.441–0.893; p = 0.001).
Figure 4.
Forest plot of the overall odds ratios for catheter removal due to catheter malfunction in the treated group vs. the control group. The random model of overall odds ratio for the need to remove the catheter for malfunction showed a significant overall effect of the interventions in reducing the risk for catheter removal compared with the control condition (OR, 0.696; 95% CI, 0.397–1.223; p = 0.208).
Figure 4.
Forest plot of the overall odds ratios for catheter removal due to catheter malfunction in the treated group vs. the control group. The random model of overall odds ratio for the need to remove the catheter for malfunction showed a significant overall effect of the interventions in reducing the risk for catheter removal compared with the control condition (OR, 0.696; 95% CI, 0.397–1.223; p = 0.208).
Figure 5.
Forest plot of the overall odds ratios for thrombolytic treatments for catheter malfunction in the treated group versus the control group. The random model of overall odds ratio for the need to administer thrombolytic treatment for catheter malfunction showed a significant overall reduced risk for receiving thrombolytic treatments with interventions as compared with the control condition (OR, 1.105; 95% CI, 0.655–1.573; p = 0.946).
Figure 5.
Forest plot of the overall odds ratios for thrombolytic treatments for catheter malfunction in the treated group versus the control group. The random model of overall odds ratio for the need to administer thrombolytic treatment for catheter malfunction showed a significant overall reduced risk for receiving thrombolytic treatments with interventions as compared with the control condition (OR, 1.105; 95% CI, 0.655–1.573; p = 0.946).
Figure 6.
Forest plot of the overall odds ratios for all-cause mortality in the treated group versus the control group. The random model of overall odds ratio for all-cause mortality rate showed a significant overall effect of the interventions in reducing mortality rate as compared with the control condition (OR, 0.909; 95% CI, 0.580–1.423; p = 0.676).
Figure 6.
Forest plot of the overall odds ratios for all-cause mortality in the treated group versus the control group. The random model of overall odds ratio for all-cause mortality rate showed a significant overall effect of the interventions in reducing mortality rate as compared with the control condition (OR, 0.909; 95% CI, 0.580–1.423; p = 0.676).
Figure 7.
Trial sequential analysis of the odds ratio for evaluation event: (a) Trial sequential analysis of catheter-related bloodstream infection. Trial sequential analysis of 17 studies with a lower risk of bias in reporting catheter-related bloodstream infection, with a control event proportion of 17%, diversity of 45%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 630,022 was not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The overall OR of CRBSI was 0.439 (95% CI, 0.290–1.668; p < 0.001); (b) trial sequential analysis of exit-site infection. Trial sequential analysis of eleven studies with low risk of bias reporting exit-site infection, with a control event proportion of 17%, diversity of 30%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 336,863 was not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The OR of ESI was 0.644 (95% CI, 0.469–0.883; p = 0.006); (c) trial sequential analysis of nine studies with a lower risk of bias reporting the need to remove the catheter for catheter malfunction, with a control event proportion of 17%, diversity of 71%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 625,306 were not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The OR of the need to remove the catheter for catheter malfunction was 0.746 (95% CI, 0.431–1.293; p = 0.151); (d) trial sequential analysis of thrombolytic treatments for catheter malfunction. Trial sequential analysis of nine studies with low risk of bias reporting the need to receive thrombolytic treatment for catheter malfunction, with a control event proportion of 17%, diversity of 91%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 615,306 were not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The OR of the need to receive thrombolytic treatment for catheter malfunction was 1.015 (95% CI, 0.655–1.573; p = 0.461); (e) trial sequential analysis of all-cause mortality. Trial sequential analysis of five studies with a lower risk of bias reporting all-cause mortality, with a control event proportion of 17%, diversity of 78%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 8419were not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The OR of all-cause mortality was 0.976 (95% CI, 0.663–1.439; p = 0.296). Notes: The solid blue line is the cumulative Z-curve. The vertical black dashed line is required information size. The green dashed lines represent the trial sequential monitoring boundaries and the futility boundaries.
Figure 7.
Trial sequential analysis of the odds ratio for evaluation event: (a) Trial sequential analysis of catheter-related bloodstream infection. Trial sequential analysis of 17 studies with a lower risk of bias in reporting catheter-related bloodstream infection, with a control event proportion of 17%, diversity of 45%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 630,022 was not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The overall OR of CRBSI was 0.439 (95% CI, 0.290–1.668; p < 0.001); (b) trial sequential analysis of exit-site infection. Trial sequential analysis of eleven studies with low risk of bias reporting exit-site infection, with a control event proportion of 17%, diversity of 30%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 336,863 was not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The OR of ESI was 0.644 (95% CI, 0.469–0.883; p = 0.006); (c) trial sequential analysis of nine studies with a lower risk of bias reporting the need to remove the catheter for catheter malfunction, with a control event proportion of 17%, diversity of 71%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 625,306 were not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The OR of the need to remove the catheter for catheter malfunction was 0.746 (95% CI, 0.431–1.293; p = 0.151); (d) trial sequential analysis of thrombolytic treatments for catheter malfunction. Trial sequential analysis of nine studies with low risk of bias reporting the need to receive thrombolytic treatment for catheter malfunction, with a control event proportion of 17%, diversity of 91%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 615,306 were not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The OR of the need to receive thrombolytic treatment for catheter malfunction was 1.015 (95% CI, 0.655–1.573; p = 0.461); (e) trial sequential analysis of all-cause mortality. Trial sequential analysis of five studies with a lower risk of bias reporting all-cause mortality, with a control event proportion of 17%, diversity of 78%, type I error of 5%, power of 80%, and relative risk reduction of 30%. The required information size of 8419were not reached and none of the boundaries for benefit, harm, or futility were crossed, leaving the meta-analysis inconclusive at a 30% relative risk reduction. The OR of all-cause mortality was 0.976 (95% CI, 0.663–1.439; p = 0.296). Notes: The solid blue line is the cumulative Z-curve. The vertical black dashed line is required information size. The green dashed lines represent the trial sequential monitoring boundaries and the futility boundaries.
Figure 8.
Funnel plot of the odds ratio for evaluation event: (a) Funnel plot of the odds ratio of catheter-related bloodstream infection. I2 value, 70.1%; p = 0.303; (b) funnel plot of the odds ratio of exit-site infection. I2 value, 28.0%; p = 0.010; (c) funnel plot of the odds ratio of catheter removal for catheter malfunction. I2 value, 55.9%; p = 0.208; (d) funnel plot of the odds ratio of thrombolytic treatments for catheter malfunction. I2 value, 88.69%; p = 0.946; (e) funnel plot of the odds ratio of all-cause mortality. I2 value, 88.6%; p = 0.804. Regarding odds ratio heterogeneity, the I2 value in both the overall studies included is indicated for each case. Egger’s test revealed the existence of significant publication bias regarding the overall odds ratios, p-value is indicated for each case.
Figure 8.
Funnel plot of the odds ratio for evaluation event: (a) Funnel plot of the odds ratio of catheter-related bloodstream infection. I2 value, 70.1%; p = 0.303; (b) funnel plot of the odds ratio of exit-site infection. I2 value, 28.0%; p = 0.010; (c) funnel plot of the odds ratio of catheter removal for catheter malfunction. I2 value, 55.9%; p = 0.208; (d) funnel plot of the odds ratio of thrombolytic treatments for catheter malfunction. I2 value, 88.69%; p = 0.946; (e) funnel plot of the odds ratio of all-cause mortality. I2 value, 88.6%; p = 0.804. Regarding odds ratio heterogeneity, the I2 value in both the overall studies included is indicated for each case. Egger’s test revealed the existence of significant publication bias regarding the overall odds ratios, p-value is indicated for each case.
Table 1.
Summary of the retrieved trials investigating experimental group and control group.
Table 1.
Summary of the retrieved trials investigating experimental group and control group.
Author, Year, Country, Reference | RCT | Total N | Treated (N) | Control (N) | QA |
---|
Buturovic et al., 1998, SI, [29] | No | 30 | 4% CiT (20) | 1666 U/mL HpR (10) | 3 # |
Dogra et al., 2002, AU, [30] | Yes | 79 | 26.7 mg/mL GM + 1.04% CiT (42) | 5000 U/mL HpR (37) | 8 * |
Betjes et al., 2004, NL, [31] | No | 58 | 1.35% TRD +4% CiT (37) | 5000 U/mL HpR (39) | 3 # |
Weijmer et al., 2005, NL, [14] | Yes | 291 | 30% CiT (148) | 5000 U/mL HpR (143) | 8 * |
Nori et al., 2006, USA, [32] | No | 40 | 4 mg/mL GM + 3.13% CiT (41) | 5000 U/mL HpR (21) | 3 # |
Lok et al., 2007, CA, [13] | No | 250 | 4% CiT (129) | 5000 U/mL HpR (121) | 3 # |
MacRae et al., 2008, CA, [12] | No | 61 | 4% CiT (32) | 5000 U/mL HpR (29) | 3 # |
Power et al., 2009, UK, [4] | Yes | 232 | 46.7% CiT (132) | 5000 U/mL HpR (100) | 8 * |
Solomon et al., 2010, UK, [33] | Yes | 107 | 1.35% TRD + 4% CiT (53) | 5000 U/mL HpR (54) | 8 * |
Filiopoulos et al., 2011, GR, [34] | Yes | 117 | 1.35% TRD + 4% CiT (119) | 5000 U/mL HpR (58) | 8 * |
Maki et al., 2011, USA, [6] | Yes | 407 | 7.0% CiT + MMP (206) | 5000 U/mL HpR (201) | 8 * |
Moran et al., 2012, USA, [8] | No | 303 | 320 μg/mL GM + 4% CiT (155) | 1000 U/mL HpR (148) | 3 # |
Chen et al., 2014, CH, [35] | Yes | 72 | 10% NaCl (36) | 3125 U/mL HpR (36) | 8 * |
Souweine et al., 2015, FR, [19] | Yes | 1460 | 60% w/w EtOH (730) | 0.9% NaCl (730) | 8 * |
Moghaddas et al., 2015, IR, [18] | Yes | 87 | 10 mg/mL TMP/SMX + 2500 U/mL HpR (46) | 2500 U/mL HpR (41) | 8 * |
Kanaa et al., 2015, UK, [17] | Yes | 115 | 4% EDTA (59) | 5000 U/mL HpR (56) | 8 * |
Zwiech et al., 2016, PL, [21] | Yes | 50 | 4% CiT (26) | 5000 U/mL HpR (24) | 8 * |
Chu et al., 2016, AU, [20] | Yes | 100 | 1000 U/mL HpR (52) | 5000 U/mL HpR (48) | 8 * |
Correa Barcellos et al., 2017, BZ, [22] | Yes | 464 | 30% CiT (231) | 5000 U/mL HpR (233) | 8 * |
Sofroniadou et al., 2017, GR, [23] | Yes | 103 | 70% w/w EtOH + UFH 2000 U/mL (52) | 2000 U/mL HpR (51) | 8 * |
Winnicki et al., 2018, Au, [24] | No | 406 | 1.35% TRD + 4% CiT + HpR (52) | 4% CiT (54) | 3 # |
Table 2.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for CRBSI.
Table 2.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for CRBSI.
Subgroup | Odds Ratio | 95% Confidence Interval |
---|
combined regimen |
RCT | 0.606 | 0.298–1.230 |
Not RCT | 0.206 | 0.058–0.730 |
Not combined regimen |
RCT | 0.417 | 0.192–0.905 |
Not RCT | 0.289 | 0.083–0.365 |
Regimen containing antibiotic |
RCT | 0.191 | 0.023–1.564 |
Not RCT | 0.136 | 0.051–0.365 |
Regimen Not containing antibiotic |
RCT | 0.546 | 0.314–0.949 |
Not RCT | 0.342 | 0.191–0.614 |
High Concentration of major regimen |
RCT | 0.644 | 0.155–2.671 |
Low Concentration of major regimen |
RCT | 0.421 | 0.186–0.956 |
Not RCT | 0.260 | 0.135–0.497 |
Table 3.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for exit site infection.
Table 3.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for exit site infection.
Subgroup | Odds Ratio | 95% Confidence Interval |
---|
combined regimen |
RCT | 0.849 | 0.358–2.011 |
Not RCT | 0.706 | 0.307–1.62 |
Not combined regimen |
RCT | 0.503 | 0.276–0.918 |
Not RCT | 0.620 | 0.113–3.389 |
Regimen containing antibiotic |
RCT | 0.571 | 0.189–1.725 |
Not RCT | 0.735 | 0.284–1.905 |
Regimen Not containing antibiotic |
RCT | 0.599 | 0.334–1.071 |
Not RCT | 0.650 | 0.246–1.722 |
High Concentration of major regimen |
RCT | 0.631 | 0.214–1.862 |
Low Concentration of major regimen |
RCT | 0.805 | 0.282–2.297 |
Not RCT | 0.692 | 0.35–1.368 |
Table 4.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for catheter removal due to catheter malfunction.
Table 4.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for catheter removal due to catheter malfunction.
Subgroup | Odds Ratio | 95% Confidence Interval |
---|
Combined regimen |
RCT | 0.520 | 0.086–3.15 |
Not RCT | 0.977 | 0.628–1.518 |
Not combined regimen |
RCT | 0.434 | 0.068–2.786 |
Not RCT | 1.106 | 0.392–3.124 |
Regimen containing antibiotic |
RCT | 0.741 | 0.087–6.287 |
Not RCT | 0.992 | 0.633–1.554 |
Regimen not containing antibiotic |
RCT | 0.329 | 0.051–2.138 |
Not RCT | 1.010 | 0.39–2.619 |
High concentration of major regimen |
RCT | 0.896 | 0.029–27.554 |
Low concentration of major regimen |
RCT | 0.479 | 0.051–4.537 |
Not RCT | 0.995 | 0.663–1.494 |
Table 5.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for the need of thrombolytic treatment for catheter malfunction.
Table 5.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for the need of thrombolytic treatment for catheter malfunction.
Subgroup | Odds Ratio | 95% Confidence Interval |
---|
Combined regimen |
RCT | 2.480 | 1.214–5.066 |
Not RCT | 0.620 | 0.382–1.004 |
Not combined regimen |
RCT | 1.320 | 0.888–1.961 |
Not RCT | 0.599 | 0.344–1.043 |
Regimen containing antibiotic |
RCT | 1.969 | 0.944–4.107 |
Not RCT | 0.620 | 0.382–1.004 |
Regimen not containing antibiotic |
RCT | 1.385 | 0.893–2.149 |
Not RCT | 0.345 | 0.108–1.102 |
High concentration of major regimen |
RCT | 1.415 | 0.784–2.554 |
Low concentration of major regimen |
RCT | 2.480 | 1.042–5.902 |
Not RCT | 0.637 | 0.518–0.783 |
Table 6.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for all-cause mortality.
Table 6.
Subgroup analysis of odds ratio based on study designs, combined regimen, regimen containing antibiotic, and concentration of regimen for all-cause mortality.
Subgroup | Odds Ratio | 95% Confidence Interval |
---|
Combined regimen |
RCT | 0.725 | 0.237–2.211 |
Not RCT | 1.579 | 0.154–16.18 |
Not combined regimen |
RCT | 0.884 | 0.404–1.933 |
Regimen containing antibiotic |
RCT | 1.506 | 0.388–5.838 |
Not RCT | 1.579 | 0.154–16.18 |
Regimen not containing antibiotic |
RCT | 0.723 | 0.367 – 1.425 |
High concentration of major regimen |
RCT | 0.669 | 0.054–8.324 |
Low Concentration of major regimen |
RCT | 0.615 | 0.09–4.22 |
Not RCT | 1.579 | 0.154–16.18 |